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NCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of All - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11875699
AU - Murray L; McCarron P; Bailie K; Middleton R; Davey Smith G; Dempsey S;
TI -
McCarthy A; Gavin A
Association of early life factors and acute lymphoblastic leukaemia in
childhood: historical cohort study.
SO - Br J Cancer 2002 Feb 1;86(3):356-61
AD - Northern Ireland Cancer Registry, Department of Epidemiology and Public
Health, The Queens University, Belfast, Riddel Hall, Stranmillis Road,
Belfast BT9 5EE, UK. l.murray@qub.ac.uk
In a historical cohort study of all singleton live births in Northern
Ireland from 1971-86 (n=434,933) associations between early life factors
and childhood acute lymphoblastic leukaemia were investigated.
Multivariable analyses showed a positive association between high
paternal age (> or =35 years) and acute lymphoblastic leukaemia
(relative risk=1.49; 95% confidence interval (CI)=0.96--2.31) but no
association with maternal age. High birth weight (> or =3500 g) was
positively associated with acute lymphoblastic leukaemia (relative
risk=1.66; 95% CI=1.18--2.33). Children of mothers with a previous
miscarriage or increased gestation (> or =40 weeks) had reduced risks of
ALL (respective relative risks=0.49; 95% CI=0.29--0.80, and 0.67; 95%
CI=0.48--0.94). Children born into more crowded households (> or =1
person per room) had substantially lower risks than children born into
less crowded homes with also some evidence of a lower risk for children
born into homes with three adults (relative risks=0.56; 95% CI=0.35-0.91
and 0.58; 95% CI=0.21-1.61 respectively). These findings indicate that
several early life factors, including living conditions in childhood and
maternal miscarriage history, influence risk of acute lymphoblastic
leukaemia in childhood. Copyright 2002 The Cancer Research Campaign
2
UI - 11748675
AU - Foliart DE; Iriye RN; Tarr KJ; Silva JM; Kavet R; Ebi KL
TI -
Alternative magnetic field exposure metrics: relationship to TWA,
appliance use, and demographic characteristics of children in a leukemia
survival study.
SO - Bioelectromagnetics 2001 Dec;22(8):574-80
AD - Public Health Institute, Berkeley, California, USA. publichealth@msn.com
The ongoing Childhood Leukemia Survival Study is examining the possible
association between magnetic field exposure and survival of children
with newly diagnosed acute lymphocytic leukemia (ALL). We report the
results of the first year 24 h personal magnetic field monitoring for
356 US and Canadian children by time weighted average TWA and
alternative exposure metrics. The mean TWA of 0.12 microT was similar to
earlier personal exposure studies involving children. A high correlation
was found between 24 h TWA and alternative metrics: 12 h day TWA, 12
night TWA, geometric mean, 95th percentile value, percentage time over
0.2 and 0.3 microT, and an estimate of field stability (Constant Field
Metric). Two measures of field intermittency, rate of change metric
(RCM) and standardized rate of change metric (RCMS), were not highly
correlated with TWA. The strongest predictor of TWA was location of
residence, with highest TWAs associated with urban areas. Residence in
an apartment, lower paternal educational level, and residential mobility
were also associated with higher TWAs. There were no significant
differences in the appliance use patterns of children with higher TWA
values. Children with the highest field intermittency (high RCM) were
more likely to sit within 3 feet of a video game attached to the TV. Our
results suggest that 24 h TWA is a representative metric for certain
patterns of exposure, but is not highly correlated with two metrics that
estimate field intermittency. Copyright 2001 Wiley-Liss, Inc.
3
UI - 11801462
AU - Bolufer P; Barragan E; Verdeguer A; Cervera J; Fernandez JM; Moreno I;
TI -
Lerma E; Esquembre C; Tasso M; Fuster V; Bermudez M; Sanz MA
Rapid quantitative detection of TEL-AML1 fusion transcripts in pediatric
acute lymphoblastic leukemia by real-time reverse transcription
polymerase chain reaction using fluorescently labeled probes.
SO - Haematologica 2002 Jan;87(1):23-32
AD - Laboratorio de Biologia Molecular, (Lab Hormonas), C Maternal Hospital
Universitario La Fe, Avda Campanar 21, 46009 Valencia, Spain.
bolufer_pas@gva.es
BACKGROUND AND OBJECTIVES: We report a new real-time reverse
transcription polymerase chain reaction (RT-PCR) method for
quantification of TEL-AML1 transcripts. The method is based on
hybridization probe (HybProbe) chemistry applied in LightCycler
equipment. The study group comprised 44 successive cases of pediatric
acute lymphoblastic leukemia (P-ALL). DESIGN AND METHODS: The
quantitative estimation of TEL-AML1 transcripts was performed in 10
P-ALL TEL-AML1-positive patients. The PCR was performed in capillary
tubes in 10 microL final volumes using two sets of primers: M1, which
detects the long (L-form) and short (S-form) transcripts, and M2,
specific for the L-form. The fluorescently labeled HybProbes (TEL 3FL
and TEL 5LC) hybridize to the TEL region. TEL-AML1 expression was
normalized relative to the levels of AML1 transcripts. Standard curves
were prepared using serial dilutions of plasmids with TEL-AML1 or AML1
inserts. RESULTS: The sensitivity attained allowed the detection of
TEL-AML1 transcripts at a 10-4 dilution of a cDNA sample from a patient
at diagnosis. The within-assay coefficient of variation (CV) for
TEL-AML1 was 7.0% and the between-assay CV was 13%. Levels of TEL-AML1
transcript and the TEL-AML1/AML1 ratio decreased by more than four log
units (p <0.001) during or after the course of initial treatment. Most
of the patients who achieved complete remission after 5-6 months of
initial treatment were TEL-AML1 negative, although some positive samples
with negligible amounts of TEL-AML1 transcripts were still detected.
INTERPRETATION AND CONCLUSIONS: This method has the sensitivity and
reliability required to monitor the presence of minimal residual
disease, and could be a powerful tool in monitoring the efficacy of the
response to chemotherapy.
4
UI - 11849208
AU - Wright AM; Paterson AR; Sowa B; Akabutu JJ; Grundy PE; Gati WP
TI -
Cytotoxicity of 2-chlorodeoxyadenosine and arabinosylcytosine in
leukaemic lymphoblasts from paediatric patients: significance of
cellular nucleoside transporter content.
SO - Br J Haematol 2002 Mar;116(3):528-37
AD - Department of Pharmacology, University of Alberta and Cross Cancer
Institute, Edmonton, Alberta, Canada.
2-chlorodeoxyadenosine (2-CdA) and arabinosylcytosine (araC) are
nucleoside drugs that are used to treat various leukaemias, although
2-CdA has not been tested extensively in children with acute
lymphoblastic leukaemia (ALL). Nucleoside cytotoxicity depends on the
conversion of these agents to 5'-phosphate derivatives, following drug
entry into cells via nucleoside transport (NT) processes. This study
compared es nucleoside transporter content, determined using a flow
cytometric assay with SAENTA
[5'-S-(2-aminoethyl)-N6-(4-nitrobenzyl)-5'-thioadenosine] fluorescein,
and cytotoxicities of 2-CdA and araC in fresh lymphoblasts from
previously untreated paediatric ALL patients and the human T-lymphoblast
cell line, CCRF-CEM. Lymphoblast samples from individual patients ranged
widely in sensitivity to both 2-CdA (IC50, 6 nmol/l to > 5 micromol/l;
mean = 418 nmol/l; n = 8) and araC (IC50, 59 nmol/l to > 5 micromol/l;
mean = 1050 nmol/l; n = 7), although IC50 values for the two drugs were
correlated (r = 0.78, P = 0.032, n = 7). Cellular es nucleoside
transporter content varied more than 35-fold among samples from 10
patients. The correlation between es nucleoside transporter content and
drug sensitivity was statistically significant for araC (r = -0.93, P =
0.023, n = 5), but not for 2-CdA (r = -0.57, P = 0.23, n = 6). Exposure
of CCRF-CEM cells to araC resulted in a substantial araC
concentration-dependent increase in the relative survival of es
transporter-deficient cells, whereas the increase was slight following
exposure to 2-CdA. We conclude that, in ALL lymphoblasts, es nucleoside
transporter content is a determinant of araC sensitivity and that a
deficiency in NT may impart resistance to araC.
5
UI - 11880754
AU - Axelson O; Fredrikson M; Akerblom G; Hardell L
TI -
Leukemia in childhood and adolescence and exposure to ionizing radiation
in homes built from uranium-containing alum shale concrete.
SO - Epidemiology 2002 Mar;13(2):146-50
AD - Division of Occupational and Environmental Medicine, Department of
Health and Environment, Linkoping University, Linkoping, Sweden.
olav.axelson@ymk.liu.se
Concerns in Sweden about indoor radon around 1980 prompted measurements
of gamma-radiation from the facades of houses to identify those
constructed of uranium-containing alum shale concrete, with potentially
high radon concentrations. To evaluate any possible risk of acute
lymphocytic leukemia from exposure to elevated gamma-radiation in these
homes, we identified the acute lymphocytic leukemia cases less than 20
years of age in Sweden during 1980-1989 as well as eight controls per
case from the population registry, matching on age, gender, and county.
Using the existing measurements, exposure was assessable for 312 cases
and 1,418 controls from 151 properly measured municipalities. A
conditional logistic odds ratio of 1.4 (95% confidence interval =
1.0-1.9) was obtained for those ever having lived in alum shale concrete
houses, with the average exposure exceeding 0.10 microsieverts per hour.
Comparing those who ever lived in alum shale concrete houses (divided by
higher and lower annual average exposure) with those who never lived in
such houses, we found a weak dose-response relation. The results suggest
some risk of acute lymphocytic leukemia from indoor ionizing radiation
among children and young adults.
6
UI - 11920508
AU - Ohnita K; Isomoto H; Mizuta Y; Maeda T; Haraguchi M; Miyazaki M; Murase
TI -
K; Murata I; Tomonaga M; Kohno S
Helicobacter pylori infection in patients with gastric involvement by
adult T-cell leukemia/lymphoma.
SO - Cancer 2002 Mar 1;94(5):1507-16
AD - Second Department of Internal Medicine, Nagasaki University School of
Medicine, Nagasaki, Japan.
BACKGROUND: Gastrointestinal involvement is seen frequently in patients
with adult T-cell leukemia/lymphoma (ATLL). The authors previously
showed a relatively low prevalence of Helicobacter pylori infection in
individuals with human T-cell lymphotropic virus 1 (HTLV-1) infection,
including patients with ATLL; however, the correlation between H. pylori
infection and ATLL gastric involvement has not been investigated.
METHODS: The authors studied 71 patients with ATLL. Gastric involvement
was confirmed by endoscopy and biopsy. H. pylori infection was detected
by serology, rapid urease test, and immunohistochemistry on biopsy
samples. The expression of adhesion molecules on ATLL cells or their
ligands on the vasculature in gastric mucosa was analyzed
immunohistochemically. The expression of mucosal addressin cell adhesion
molecule 1 (MAdCAM-1) was detected by reverse transcriptase-polymerase
chain reaction (RT-PCR) analysis. RESULTS: Gastric involvement was
detected in 21 patients (30%), including 8 patients with acute clinical
subtype ATLL and 13 patients with lymphoma type ATLL. The prevalence of
H. pylori infection was 86% (18 of 21 patients) in the patients with
gastric involvement but only 38% (19 of 50 patients) in the patients
without such involvement (P < 0.001). The expression of lymphocyte
function-associated antigen 1 (LFA-1) and its ligand, intercellular
adhesion molecule 1 (ICAM-1), was most frequent on ATLL cells
infiltrating the stomach and was enhanced substantially on vascular
endothelium in H. pylori-infected gastric mucosa. Human mucosal
lymphocyte antigen 1 also was expressed on infiltrating ATLL cells in
the stomach. The expression of MAdCAM-1 mRNA assessed by RT-PCR also was
seen selectively in H. pylori-infected patients. CONCLUSIONS: ATLL cells
infiltrate gastric tissues infected with H. pylori, probably through the
interaction of adhesion molecules on these cells and their ligands on
the vasculature, i.e., through the LFA-1/ICAM-1 pathway. Copyright 2002
American Cancer Society.
7
UI - 11920481
AU - Heerema NA; Sather HN; Sensel MG; La MK; Hutchinson RJ; Nachman JB;
TI -
Reaman GH; Lange BJ; Steinherz PG; Bostrom BC; Gaynon PS; Uckun FM
Abnormalities of chromosome bands 15q13-15 in childhood acute
lymphoblastic leukemia.
SO - Cancer 2002 Feb 15;94(4):1102-10
AD - The Ohio State University Medical Center, Department of Pathology,
Columbus, Ohio, USA. heerema-1@medctr.osu.edu
BACKGROUND: Recurring breakpoints in chromosome bands 15q13-15 occur
infrequently in leukemia. To the authors' knowledge, the clinical
significance of these breakpoints in childhood acute lymphoblastic
leukemia (ALL) has not been previously investigated. METHODS: Centrally
reviewed karyotypes of children with newly diagnosed ALL enrolled on
Children's Cancer Group protocols from 1988 to 1995 formed the basis of
the current report. Statistical analyses used chi-square tests for
homogeneity of proportions, and outcome was analyzed using life table
methods and associated statistics. RESULTS: Of 1946 cases with centrally
reviewed and accepted cytogenetic analyses, 23 cases (1%) had
breakpoints in chromosome bands 15q13-15. Most patients with 15q13-15
breakpoints had standard risk ALL, although breakpoints in 15q13-15
occurred more frequently in infants than in older children. The majority
of these patients (16 patients; 70%) had balanced 15q13-15
rearrangements. Additional chromosomal abnormalities not involving 15q
included abnormal 12p, abnormal 9p, Philadelphia chromosome, deletion
6q, and an 11q23 breakpoint. Thirteen (57%) 15q13-15 breakpoints
occurred in pseudodiploid karyotypes; five (22%) were in hyperdiploid
karyotypes with 47-50 chromosomes; two (9%) were in hyperdiploid
karyotypes with > 50 chromosomes; and three (13%) were in hypodiploid
karyotypes. Of the 23 patients with 15q13-15 breakpoints, 21 were
survivors, 18 survived event-free for 2.2-9.3 years, and 3 were alive 1
to 3 years after a relapse at time of writing. CONCLUSIONS: The current
study suggests that genes at 15q13-15 may be involved in the
leukemogenesis of some cases of childhood ALL, but that with current
intensive therapy such aberrations do not confer increased risk of
treatment failure. Copyright 2002 American Cancer Society. DOI
10.1002/cncr.10325
8
UI - 11807640
AU - de Haas V; Vet RJ; Verhagen OJ; Kroes W; van den Berg H; van der Schoot
TI -
CE
Early detection of central nervous system relapse by polymerase chain
reaction in children with B-precursor acute lymphoblastic leukemia.
SO - Ann Hematol 2002 Jan;81(1):59-61
9
UI - 10049045
AU - Pongers-Willemse MJ; Seriu T; Stolz F; d'Aniello E; Gameiro P; Pisa P;
TI -
Gonzalez M; Bartram CR; Panzer-Grumayer ER; Biondi A; San Miguel JF; van
Dongen JJ
Primers and protocols for standardized detection of minimal residual
disease in acute lymphoblastic leukemia using immunoglobulin and T cell
receptor gene rearrangements and TAL1 deletions as PCR targets: report
of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual
disease in acute leukemia.
SO - Leukemia 1999 Jan;13(1):110-8
AD - Department of Immunology, University Hospital Rotterdam/Erasmus
University Rotterdam, The Netherlands.
It is now widely accepted that the detection of minimal residual disease
(MRD) has prognostic value in acute leukemia. However clinical MRD
studies need standardized techniques. Therefore, several European
laboratories have aligned their goals and performed comparative studies
to achieve optimization and standardization of MRD techniques. This was
achieved via the BIOMED-1 Concerted Action "Investigation of minimal
residual disease in acute leukemia: International standardization and
clinical evaluation." This report describes the development of PCR
primers and protocols for the detection of MRD in acute lymphoblastic
leukemia (ALL) using clone-specific junctional regions of immunoglobulin
and T cell receptor gene rearrangements and TAL1 deletions as PCR
targets. A total of 54 primers was developed (1) to amplify
rearrangements of the TCRD, TCRG, and IGK (Kde) genes as well as TAL1
deletions; (2) to sequence the junctional regions and breakpoint fusion
regions; and (3) to perform MRD detection in bone marrow or peripheral
blood samples during follow-up of ALL patients. Protocols were
established to identify PCR targets at diagnosis by performing 25 PCR
reactions per patient using appropriate positive and negative controls.
Standardized protocols were developed for MRD monitoring via single
amplification of the PCR target followed by dot blot hybridization with
the corresponding patient-specific junctional region probe. In addition,
alternative approaches were designed for cases where the target
sensitivity of at least 10(-4) was not obtained. The standardization
described here of MRD-PCR techniques is essential for the process of
translating MRD research into clinical practice.
10
UI - 10803512
AU - Porwit-MacDonald A; Bjorklund E; Lucio P; van Lochem EG; Mazur J;
TI -
Parreira A; van den Beemd MW; van Wering ER; Baars E; Gaipa G; Biondi A;
Ciudad J; van Dongen JJ; San Miguel JF; Orfao A
BIOMED-1 concerted action report: flow cytometric characterization of
CD7+ cell subsets in normal bone marrow as a basis for the diagnosis and
follow-up of T cell acute lymphoblastic leukemia (T-ALL).
SO - Leukemia 2000 May;14(5):816-25
AD - Department of Pathology, Karolinska Hospital, Stockholm, Sweden.
The European BIOMED-1 Concerted Action was initiated in 1994 to improve
and standardize the flow cytometric detection of minimal residual
disease (MRD) in acute leukemia (AL). Three different protocols were
defined to identify the normal subsets of B, T and myeloid cells in bone
marrow (BM), and were applied to the different types of AL in order to
study aberrant immunophenotypes. Using sensitive acquisition methods
('live gate') T cell subsets in normal BM could be identified with five
triple-stains: CD7/CD5/CD3, CD7/CD4/CD8, CD7/CD2/CD3, CD7/CD38/CD34 and
TdT/CD7/surface or cytoplasmic (cy)CD3 (antibodies conjugated with
FITC/PE/PECy5 or PerCP, respectively). The identification of T cell
subsets in BM allowed definition of 'empty spaces' (ie areas of flow
cytometric plots where normally no cells are found). All studied T-ALL
cases (n = 65) were located in 'empty spaces' and could be discriminated
from normal T cells. The most informative triple staining was
TdT/CD7/cyCD3, which was aberrant in 91% of T-ALL cases. In most cases,
two or more aberrant patterns were found. Apparently the
immunophenotypes of T-ALL differ significantly from normal BM T cells.
This is mostly caused by their thymocytic origin, but also the
neoplastic transformation might have affected antigen expression
patterns. Application of the five proposed marker combinations in T-ALL
contributes to standardized detection of MRD, since cells persistent or
reappearing in the 'empty spaces' can be easily identified in follow-up
BM samples during and after treatment.
11
UI - 10865981
AU - Delabesse E; Burtin ML; Millien C; Madonik A; Arnulf B; Beldjord K;
TI -
Valensi F; Macintyre EA
Rapid, multifluorescent TCRG Vgamma and Jgamma typing: application to T
cell acute lymphoblastic leukemia and to the detection of minor clonal
populations.
SO - Leukemia 2000 Jun;14(6):1143-52
AD - Biological Hematology, Hopital Necker-Enfants Malades and Universite
Paris V, France.
Detection of clonal T cell receptor gamma (TCRG) gene rearrangements by
PCR is widely used in both the diagnostic assessment of
lymphoproliferative disorders and the follow-up of acute lymphoblastic
leukaemia (ALL), when residual positivity in excess of 10(-3) at
morphological complete remission is increasingly recognised to be an
independent marker of poor prognosis. This is largely based on specific
detection of V-J rearrangements from childhood cases. We describe rapid,
multifluorescent Vgamma and Jgamma PCR typing of multiplex amplified
diagnostic samples, as applied to 46 T-ALL. These strategies allow
selected analysis of appropriate cases, immediate identification of
Vgamma and Jgamma segments in over 95% of alleles, improved resolution
and precision sizing and a sensitivity of detection at the 10(-2)-10(-3)
level. We demonstrate preferential V-J combinations but no difference in
V-J usage between children and adults, nor between SIL-TAL1-negative and
-positive cases. A combination of fluorescent multiplex and
Vgamma-Jgamma-specific monoplex follow-up, as described here, will allow
detection of both significant clonal evolution and of the diagnostic
clone at a level of prognostic significance, by techniques which can
readily be applied to large-scale prospective studies for which
real-time analysis is required.
12
UI - 10914544
AU - Szczepanski T; Langerak AW; Willemse MJ; Wolvers-Tettero IL; van Wering
TI -
ER; van Dongen JJ
T cell receptor gamma (TCRG) gene rearrangements in T cell acute
lymphoblastic leukemia refelct 'end-stage' recombinations: implications
for minimal residual disease monitoring.
SO - Leukemia 2000 Jul;14(7):1208-14
AD - Department of Immunology, University Hospital Rotterdam/Erasmus
University Rotterdam, The Netherlands.
The T cell receptor gamma (TCRG) gene configuration was established in a
large series of 126 T cell acute lymphoblastic leukemia (T-ALL) patients
using combined Southern blotting (SB) and heteroduplex PCR analyses. The
vast majority of TALL (96%) displayed clonal TCRG gene rearrangements,
with biallelic recombination in 91% of patients. A small immature
subgroup of CD3- T-ALL (n = 5) had both TCRG genes in germline
configuration, three of them having also germline TCRD genes. In five
patients (4%) combined SB and PCR results indicated oligoclonality. In
five rearrangements detected by SB, the Vgamma gene segment could not be
identified suggesting illegitimate recombination. Altogether, 83% of
TCRG gene rearrangements involved either the most upstream Vgamma2 gene
(including four cases with interstitial deletion of 170 bp in Vgamma2)
and/or the most downstream Jgamma2.3 segment, which can be perceived as
'end-stage' recombinations. Comparative analysis of the TCRG gene
configuration in the major immunophenotypic subgroups indicated that
TCRgammadelta+ T-ALL display a less mature immunogenotype as compared to
TCRalphabeta+ and most CD3- cases. This was reflected by a significantly
increased usage of the more downstream Vgamma genes and the upstream
Jgamma1 segments. Comparison between adult and pediatric T-ALL patients
did not show any obvious differences in TCRG gene configuration. The
high frequency, easy detectability, rare oligoclonality, and frequent
'end-stage' recombinations make TCRG gene rearrangements principal
targets for PCR-based detection of minimal residual disease (MRD) in
T-ALL. We propose a simple heteroduplex PCR strategy, applying five
primer combinations, which results in the detection of approximately 95%
of all clonal TCRG gene rearrangements in T-ALL. This approach enables
identification of at least one TCRG target for MRD monitoring in 95% of
patients, and even two targets in 84% of T-ALL.
13
UI - 11480575
AU - van Wering ER; van der Linden-Schrever BE; van der Velden VH;
TI -
Szczepanski T; van Dongen JJ
T-lymphocytes in bone marrow samples of children with acute
lymphoblastic leukemia during and after chemotherapy might hamper
PCR-based minimal residual disease studies.
SO - Leukemia 2001 Aug;15(8):1301-3
14
UI - 11914187
AU - Reynolds P; Von Behren J; Elkin EP
TI -
Birth characteristics and leukemia in young children.
SO - Am J Epidemiol 2002 Apr 1;155(7):603-13
AD - California Department of Health Services, Environmental Health
Investigations Branch, Oakland, CA 94612, USA. preynold@dhs.ca.gov
The relation between birth characteristics and leukemia in young
children was investigated in a large population-based study in
California. Cases were obtained from the statewide cancer registry for
1988-1997. During this time, 1,957 leukemia cases were diagnosed among
children under age 5 years. Of these, 1,728 (88%) were matched to a
California birth certificate. Two control birth certificates, matched on
date of birth and sex, were randomly selected from the statewide birth
registry for each case. Analyses were performed separately for acute
lymphoid leukemia (ALL) and acute nonlymphoid leukemia (ANLL). Odds
ratios and 95% confidence intervals were estimated from conditional
logistic regression. The strongest finding was for greatly increased
risk of both types of leukemia in children with Down's syndrome (22
cases and no controls). African-American children had strikingly
decreased risk for ALL (odds ratio (OR) = 0.29, 95% confidence interval
(CI): 0.20, 0.42), and Asian/Pacific Islanders had increased risk for
ANLL (OR = 2.00, 95% CI: 1.19, 3.36). Older maternal age was associated
with slightly increased risk for ALL (maternal age > or =35 years, OR =
1.25, 95% CI: 1.04, 1.52), although this odds ratio was somewhat reduced
when adjusted for other factors. No strong relations were observed for
birth weight and ALL or ANLL.
15
UI - 10673739
AU - Kaleem Z; Shuster JJ; Carroll AJ; Borowitz MJ; Pullen DJ; Camitta BM;
TI -
Zutter MM; Watson MS
Acute lymphoblastic leukemia with an unusual t(8;14)(q11.2;q32): a
Pediatric Oncology Group Study.
SO - Leukemia 2000 Feb;14(2):238-40
AD - Division of Surgical Pathology, Washington University School of
Medicine, St Louis, MO, USA.
We present the clinicopathologic findings and survival data on 10
patients with acute lymphoblastic leukemia (ALL) and a rare
t(8;14)(q11.2;q32). There were five male and five female patients, nine
Caucasians and one Black, aged 4-17 (median 10.9) years. Three had Down
syndrome. Eight (80%) patients had a white blood cell (WBC) count <50 x
109/l at presentation. No patient had central nervous system involvement
or a mediastinal mass. Two patients had concurrent splenomegaly and
hepatomegaly. Adenopathy was absent in four, minimal in three, moderate
in one and prominent in two patients. All eight cases where
immunophenotyping was performed by flow cytometry showed a B-precursor
phenotype with expression of CD10 (CALLA). Only one case exhibited
t(8;14)(q11.2;q32) as the sole karyotypic abnormality. Three patients
were classified as standard-risk and seven high-risk by NCI (National
Cancer Institute) consensus risk group categories. All patients achieved
complete remission and seven patients were in complete continuous
remission (CCR) after chemotherapy designed for B-precursor ALL. Three
patients relapsed after 23.5, 31.3 and 32.1 months of EFS; the first
patient also had t(9;22)(q34;q11), the second had a WBC count of 126 x
109/l at presentation while the third patient had no high risk features
except for age 10 years. Thus, from our data, the t(8;14)(q11.2;q32)
does not appear to confer an increased risk of relapse. Further
observations are needed to confirm this conclusion.
16
UI - 11789265
AU - Tan H; Hao Y; Ying H
TI -
[Study on human leukemia cell apoptosis inducing effect of fraction C of
Naja naja Actra Venom]
SO - Zhongguo Zhong Xi Yi Jie He Za Zhi 2000 Apr;20(4):272-5
AD - Second Affiliated Hospital of Guangzhou Medical College, Guangzhou
(510260).
OBJECTIVE: To study the effect and mechanism of fraction C isolated from
Naja naja Actra Venom (FCNNAV) in inducing apoptosis of human leukemia
cells. METHODS: Light microscope, transmission electron microscope, DNA
electrophoresis, flow cytometry and RT-PCR assay were used to observe
the changes of human leukemia cells in morphology and biochemistry, and
Bcl-2/Bax expression after exposing to FCNNAV. RESULTS: FCNNAV could
induce HL60 cells apoptosis demonstrated by the typical morphological
and biochemical changes. Flow cytometry showed that J6-1, K562, HL60 and
fresh leukemia cells apoptosis could be induced by FCNNAV, and the
apoptosis rate was dose-dependent. RT-PCR detection showed the Bcl-2
gene expression of HL60 cells was down-regulated by FCNNAV, whereas the
Bax expression was unaffected. CONCLUSION: FCNNAV could induce apoptosis
of human leukemia cells and this effect is related to down-regulation of
Bcl-2 gene expression level.
17
UI - 11915569
AU - Vilmer E; Dhedin N
TI -
[Acute lymphoblastic leukemia]
SO - Rev Prat 2002 Jan 15;52(2):213-7
AD - Service d'hemato-immunologie pediatrique, hopital Robert-Debre, APHP,
75019 Paris.
18
UI - 7812006
AU - Madsen PS; Hokland P; Clausen N; Ellegaard J; Hokland M
TI -
Differential expression levels of the heat shock protein 27 isoforms in
pediatric normal, nonleukemic and common acute lymphoblastic leukemia
B-cell precursors.
SO - Blood 1995 Jan 15;85(2):510-21
AD - University Department of Medicine and Hematology, Aarhus Amtssygehus,
Denmark.
Heat shock protein 27 (hsp27) may function as a regulator of
microfilament dynamics and may participate in signal transduction
pathways of different cell growth regulators, with the mitogen-activated
protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme
responsible for its phosphorylation. Using two-dimensional gel
electrophoresis, we have compared the expression levels of two hsp27
isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD;
isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric
point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs)
purified from either common acute lymphoblastic leukemia (c-ALL)
patients, normal donors, or non-c-ALL patients. Compared with normal
BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5
to 9 of mean level) in c-ALL as well as in non-c-ALL (nonleukemic)
precursors. Though increased phosphorylation of hsp27 (M3 isoform) was
observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean
level compared with normal BCPs and precursors from c-ALL at diagnosis),
which might represent a differential enzymatic activity, this was not
distinguishable from that of non-c-ALL patients. Therefore, our studies
suggest constitutive differences of hsp27 isoforms between pediatric
leukemic BCPs and their relatively low-expressing, immunophenotypically
normal bone marrow counterparts. In light of the occasional and possibly
transient increase of hsp27 expression during nonleukemic BCP
differentiation and the possible role of hsp27 in signal transduction to
microfilaments, these differences might be of considerable biologic
interest and of importance in future studies of regulated normal or
dysregulated leukemic hematopoietic cellular differentiation.
19
UI - 9447846
AU - van der Reijden BA; Bloomfield CD; Touw IP; Jansen JH
TI -
Acute leukemias with structurally altered core binding factor subunits
Netherlands.
SO - Leukemia 1997 Dec;11(12):2217-9
AD - Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
In the summer of 1997, the first meeting on 'Acute Leukemias with
Structurally Altered Core Binding Factor Subunits' was held. During the
meeting, which attracted more than 140 participants, many recognized
experts in the field of CBF and leukemia were present. In this short
report we summarize new data on CBF involvement in leukemia and other
diseases that were presented during the meeting.
20
UI - 9573029
AU - Tanaka Y; Mine S; Figdor CG; Wake A; Hirano H; Tsukada J; Aso M; Fujii
TI -
K; Saito K; van Kooyk Y; Eto S
Constitutive chemokine production results in activation of leukocyte
function-associated antigen-1 on adult T-cell leukemia cells.
SO - Blood 1998 May 15;91(10):3909-19
AD - The First Department of Internal Medicine , University of Occupational
and Environmental Health, Japan.
Adult T-cell leukemia (ATL) is characterized by massive infiltration of
circulating ATL cells into a variety of tissues, a finding often
associated with poor prognosis. Leukocyte migration from circulation
into tissue depends on integrin-mediated adhesion to endothelium, and
integrins are tightly regulated by several stimuli, such as inflammatory
chemokines. However, the exact mechanisms that enhance adherence of
leukemic cells to the endothelium and infiltration into tissues remain
to be fully understood. We investigated the mechanisms of extravasation
of leukemic cells using ATL cells and report the following novel
features of endogenous chemokine-induced adhesion of ATL cells to the
endothelium. ATL cells spontaneously adhered to endothelial cells
without exogenous stimulation. Integrin leukocyte function-associated
antigen-1 (LFA-1) on ATL cells was spontaneously activated. ATL cells
produced high amounts of chemokines, macrophage inflammatory
protein-1alpha (MIP-1alpha), and MIP-1beta. Adhesion of ATL cells to
endothelial cells and the expression of activated form of LFA-1 were
reduced by pretreatment with pertussis toxin, wortmannin, or
anti-MIP-1alpha and MIP-1beta antibodies or transfection with antisense
of MIP-1alpha or MIP-1beta. Spontaneous polymerization of cytoskeletal
F-actin was observed in ATL cells, which was also inhibited by pertussis
toxin and wortmannin. We propose that ATL cells adhere to endothelial
cells through an adhesion cascade similar to normal leukocytes and that
the chemokines produced by ATL cells are involved in triggering integrin
LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent
activation of phosphoinositide 3-kinases in an autocrine manner. These
events result in a strong adhesion of ATL cells to the endothelium and
spontaneous transendothelial migration.
21
UI - 10079288
AU - Thorpe KL; Schafer AJ; Genin E; Trowsdale J; Beck S
TI -
Detection of polymorphism in the RING3 gene by high-throughput
fluorescent SSCP analysis.
SO - Immunogenetics 1999 Apr;49(4):256-65
AD - The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge,
CB10 1SA, UK.
We describe the use of a high-throughput, fluorescent,
polymorphism-detection system, based on single-strand conformation
polymorphism to screen for polymorphism in the RING3 gene. This is the
first extensive mutation screen of this major histocompatibility
complex-linked gene, and the entire coding region and intron-exon
junctions were examined by multiplexing over 3000 polymerase chain
reaction products. These techniques should be applicable for analysis of
variation in other human genes. Investigation of DNA from acute
lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML)
patients, as well as healthy individuals revealed low levels of
polymorphism across the RING3 gene. Comparison of the distribution of
genotypes at each polymorphic site between patients and healthy
individuals revealed a single site which significantly deviates from
Hardy-Weinberg proportions.
22
UI - 10500837
AU - Matheson EC; Hall AG
TI -
Expression of DNA mismatch repair proteins in acute lymphoblastic
leukaemia and normal bone marrow.
SO - Adv Exp Med Biol 1999;457():579-83
AD - LRF Molecular Pharmacology Group, CRU, Medical School,
Newcastle-Upon-Tyne.
Errors during normal DNA synthesis may produce mismatched base pairs.
6-Mercaptopurine (6MP), given during continuing therapy in acute
lymphoblastic leukaemia (ALL), undergoes intracellular activation to
give cytotoxic thioguanine nucleotides which are then incorporated into
the DNA of dividing cells in place of guanine. Cell death is thought to
result from futile attempts at mismatch repair. Previous work has shown
that cell lines with a defect in this pathway develop tolerance to
incorporated 6-thioguanine bases. In order to investigate the possible
relevance of mismatch repair to the chemosensitivty of blasts to 6MP,
relative to normal tissues, we have measured the expression of the
mismatch repair proteins MLH1, MSH2, PMS2 and MSH6 in blasts from
children and adults with ALL and in normal bone marrows, using western
blotting. Fifty cases of childhood ALL, 22 cases of adult ALL and 7
normal marrows have been studied. Expression of MSH2, and of MLH1 in all
but three cases, was detectable in all the blasts studied. Noticeably,
expression of MLH1 was not detected in any of the normal marrow samples.
MSH2 was detected in 4 of the normal marrows. Expression of PMS2 was not
detected in 29 cases of ALL and, like MLH1, was absent from each of the
normal marrow samples. In contrast, MSH6 was detected in all of the
normal marrows and all but 16 of the cases of ALL. There was no
difference in expression between adults and children. These results may
help to explain the relative sensitivity of leukaemic blasts to
thiopurines at presentation as compared to normal bone marrow.
23
UI - 11406533
AU - Cazzaniga G; Daniotti M; Tosi S; Giudici G; Aloisi A; Pogliani E;
TI -
Kearney L; Biondi A
The paired box domain gene PAX5 is fused to ETV6/TEL in an acute
lymphoblastic leukemia case.
SO - Cancer Res 2001 Jun 15;61(12):4666-70
AD - Clinica Pediatrica, Universita di Milano-Bicocca, Ospedale San Gerardo,
20052 Monza, Italy.
The PAX5 gene, encoding the B-cell-specific activator protein, is a
critical determinant of commitment to the B-lymphocyte pathway. This
gene, mapped at 9p13, is juxtaposed to the immunoglobulin heavy chain
(IgH) gene as a result of the t(9;14)(p13;q32), a rare but recurring
translocation found in a subset of B-cell non-Hodgkin's lymphoma cases.
In all of these, this translocation results in deregulated expression of
the gene product because of the proximity of IgH. We present here the
molecular characterization of a previously reported acute lymphoblastic
leukemia case carrying a t(9;12)(q11;p13) translocation. Using 5' rapid
amplification of cDNA ends PCR, a novel chimeric transcript was
identified that contained the NH(2)-terminal region of PAX5 and most of
the ETV6/TEL gene on 12p13. According to the fusion transcript, the
resulting chimeric protein would retain the PAX5 paired-box domain and
both the helix-loop-helix and DNA binding domains of TEL. Thus, it is
reasonable to hypothesize that this protein could act as an aberrant
transcription factor. This is the first report of PAX5 rearrangement in
a human malignancy resulting in a chimeric transcript.
24
UI - 11886378
AU - Konig M; Reichel M; Marschalek R; Haas OA; Strehl S
TI -
A highly specific and sensitive fluorescence in situ hybridization assay
for the detection of t(4;11)(q21;q23) and concurrent submicroscopic
deletions in acute leukaemias.
SO - Br J Haematol 2002 Mar;116(4):758-64
AD - Children's Cancer Research Institute (CCRI), St. Anna Kinderspital,
Vienna, Austria.
The translocation t(4;11)(q21;q23) is one of the most frequent 11q23
abnormalities associated with infant leukaemia as well as topoisomerase
inhibitor-induced secondary leukaemias. On the molecular level, the MLL
gene on 11q23 is fused to the AF4 gene in the 4q21 region, resulting in
a chimaeric MLL/AF4 fusion transcript. These particular chromosome
rearrangements are generally considered to be associated with poor
prognosis, and therefore accurate detection at diagnosis is of clinical
significance. In this study we developed a highly specific dual-colour
fluorescence in situ hybridization (FISH) assay for the detection of the
t(4;11) and demonstrate its usefulness for interphase molecular
cytogenetics. In our approach, differentially labelled genomic clones
that span the breakpoint cluster regions of both genes involved in the
specific translocation were used. Thus, t(4;11)-positive nuclei will
display two fusion signals and for t(4;11) cases with concurrent 3' MLL
deletions only one fusion signal will be displayed. A very low
false-positive value of less than 0.1% was obtained for interphase cells
with two fusion signals. In contrast, in cases with 3' MLL deletions
that display only one fusion signal, the rate of false-positive nuclei
was 10.4%. This FISH assay enables the screening of larger series of
patients with haematological diseases for t(4;11) translocations and
allows the unambiguous detection of associated cryptic deletions.
25
UI - 11902302
AU - Meshinchi S; Thomson B; Finn L S; Leisenring W; Green C; Radich J P;
TI -
Loken M; Hawkins D
Comparison of multidimensional flow cytometry with standard morphology
for evaluation of early marrow response in pediatric acute lymphoblastic
leukemia.
SO - J Pediatr Hematol Oncol 2001 Dec;23(9):585-90
AD - Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024,
USA. smeshinc@fhcrc.org
PURPOSE: We compared multidimensional flow cytometry (MDF) with
morphology in evaluating early marrow response to induction chemotherapy
in pediatric ALL. METHODS: Chemotherapy response was determined by
standard morphology or by MDF assessed by residual leukemic cell
percentage remaining in the marrow on days 7, 14, and 28 of induction.
Bone marrow response was classified as M3 (>25% leukemic blasts) or
M1/M2 (< or = 25% leukemic blasts). Multidimensional flow cytometry
evaluation was compared with that of standard morphology. Available
day-7 and day-14 marrow slides were also reevaluated by a single
pathologist without patients' clinical information. RESULTS: Of 46 day-7
specimens, eight (17%) had discordant MDF and morphologic results (P <
0.001), including six classified as M3 by morphology but were M1/M2 by
MDF, and two were classified as M3 by MDF but were M1/M2 by morphology.
Of 24 day-14 bone marrow specimens, five (20.5%) were discordant (P <
0.001), including two classified as M3 by morphology but were M1/M2 by
MDF, and three were classified as M3 by MDF but were M1/M2 by
morphology. Reevaluation of the blinded day-7 and day-14 marrow slides
yielded discordance between repeated pathology readings of 11% (P <
0.001) and 6% (P = 0.04), respectively. CONCLUSION: Our data show
significant discordance between the morphologic and MDF evaluation of
early marrow response. Early response to therapy is a significant
prognostic indicator in pediatric acute lymphoblastic leukemia and is
used to alter subsequent treatment; thus, precise assessment of response
is important. A larger comparison of MDF with morphology for the
evaluation of early response, including correlation with clinical
outcome, is warranted.
26
UI - 11843292
AU - Tsuchiya T; Hagihara M; Shimakura Y; Ueda Y; Gansuvd B; Munkhbat B;
TI -
Inoue H; Tazume K; Kato S; Hotta T
The generation of immunocompetent dendritic cells from CD34+ acute
myeloid or lymphoid leukemia cells.
SO - Int J Hematol 2002 Jan;75(1):55-62
AD - Department of Hematology and Rheumatology, Tokai University School of
Medicine, Isehara, Kanagawa, Japan.
The ability of CD34+ leukemic cells to differentiate to dendritic cells
(DCs) was investigated in 18 acute myeloid leukemia (AML) and 4 lymphoid
leukemia (ALL) patients. The generation of DCs was determined by the
expression of DC-associated CD1a or CD83 (more than 30%) with
costimulatory molecules, by CD80 antigens (>20%), and by the exhibition
of allostimulatory activity. In the AML patients, allostimulatory mature
DCs were generated from 3 of 9 M0 or M1, 2 of 5 M2,2 of 4 M4 or M5, and
3 of 4 ALL (L2) cases. In total, DCs were more efficiently induced from
cases expressing over 75% of CD34+ among whole bone marrow mononuclear
cells (8 of 12), compared with those under 75% (2 of 10; P < .05).
B-cell (CD19), natural killer (NK)-cell (CD56), or T-cell (CD7) lineage
markers, which were aberrantly expressed on the blasts, were rarely
found on leukemic DCs at the end of the culture period, and myeloid
(CD13, CD33), not lymphoid (CD10), markers were shown on ALL-derived
DCs. In Philadelphia chromosome-positive ALL or AML patients with t
(8;21), DCs were confirmed to be of leukemic origin by fluorescence in
situ hybridization analysis.
27
UI - 11823363
AU - Greaves M
TI -
Childhood leukaemia.
SO - BMJ 2002 Feb 2;324(7332):283-7
AD - Leukaemia Research Fund Centre, Institute of Cancer Research, Chester
Beatty Laboratories, London SW3 6JB. m.greaves@icr.ac.uk
28
UI - 11830473
AU - Nyvold C; Madsen HO; Ryder LP; Seyfarth J; Svejgaard A; Clausen N;
TI -
Wesenberg F; Jonsson OG; Forestier E; Schmiegelow K; The Nordic Society
for Pediatric Hematology and Oncology
Precise quantification of minimal residual disease at day 29 allows
identification of children with acute lymphoblastic leukemia and an
excellent outcome.
SO - Blood 2002 Feb 15;99(4):1253-8
AD - Department of Clinical Immunology and Department of Pediatrics, National
University Hospital, Rigshospitalet, Copenhagen, Denmark.
The postinduction level of minimal residual disease (MRD) was quantified
with a competitive polymerase chain reaction (PCR) technique in 104
children with acute lymphoblastic leukemia (ALL) diagnosed between June
significant correlation was found between the MRD level on day 15 (D15)
and day 29 (D29) after the start of induction therapy (r(s) = 0.70, P
<.0001). The 15 patients with T-cell disease had higher D29 MRD than
those with B-lineage ALL (P =.01). Age was positively related to D29 MRD
(r(s) = 0.32, P =.001). The 16 patients who had a relapse had higher D15
and D29 MRD levels than the patients who stayed in remission (median
levels D15, 1% versus 0.1%, P =.03; D29, 0.4% versus 0.01%, P =.0001).
No patients with a MRD level less than 0.01% on D29 have so far had a
relapse, whereas the 7-year probability of event-free survival for
patients with higher MRD levels was 0.52 (P =.0007). The group of
patients with a D29 MRD less than 0.01% included patients with T-cell
disease, white blood cell count more than 50 x 10(9)/L at diagnosis, or
age 10 years or older, and could not be identified by up-front criteria.
The best-fit Cox model to predict the risk of relapse included D29 MRD
(P =.004) and age (P =.009). These findings indicate that with the
present treatment protocol MRD quantification at an early stage of
therapy identifies patients with a very low risk of relapse. Further
trials are needed to reveal whether such patients with D29 MRD less than
0.01% can be cured with less intensive chemotherapy, which would reduce
the risk of serious late effects as well as the costs of therapy.
29
UI - 11830485
AU - Mori N; Sato H; Hayashibara T; Senba M; Hayashi T; Yamada Y; Kamihira S;
TI -
Ikeda S; Yamasaki Y; Morikawa S; Tomonaga M; Geleziunas R; Yamamoto N
Human T-cell leukemia virus type I Tax transactivates the matrix
metalloproteinase-9 gene: potential r
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