Table of Contents
1
UI - 11908271
AU - Stav K; Leibovici D; Siegel YI; Lindner A
TI -
Leukemoid reaction associated with transitional cell carcinoma.
SO - Isr Med Assoc J 2002 Mar;4(3):223-4
AD - Department of Urology, Assaf Harofeh Medical Center, Zerifin, Israel.
2
UI - 11801479
AU - Zamora L; Lloveras E; Espinet B; Munoz C; Perez C; Plaja A
TI -
Is the gain of 9p involved in the pathogenesis of polycythemia vera? A
purpose of a case.
SO - Haematologica 2002 Jan;87(1):ECR05
AD - Departament de Citogenetica, General-lab., Laboratoris d'analisis, C/
Londres, 45, 08036 Barcelona, Spain. e0037@imas.imim.es
3
UI - 11849213
AU - Petti MC; Latagliata R; Spadea T; Spadea A; Montefusco E; Aloe Spiriti
TI -
MA; Avvisati G; Breccia M; Pescarmona E; Mandelli F
Melphalan treatment in patients with myelofibrosis with myeloid
metaplasia.
SO - Br J Haematol 2002 Mar;116(3):576-81
AD - Ematologia, Istituto Regina Elena, Rome, Italy. rob.lati@libero.it
symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic
enlargement >5 cm and/or transfusional requirement or Hb < 10 g/dl
and/or white blood cell (WBC) count >20 x 10(9)/l and/or platelets >1.0
x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate
the efficacy and toxicity of this approach. Among 99 evaluable patients,
66 (66.7%) achieved a response after a median time of 6.7 months: 26
(26.3%) had a normalization of all clinical and haematological
parameters (complete response, CR) and 40 (40.4%) showed an improvement
>50% (partial response, PR). Thirty-three patients (33.3%) were
resistant. Reversible haematological toxicity was the most common
complication. Median durations of CR and PR were 28.4 and 26 months
respectively: median survival of CR + PR patients was 71.2 months
(95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the
non-responders (log-rank test, P =0.002). In the multivariate analysis,
the following variables were significantly associated with a shorter
survival: anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR
= 2.4) and not achieving any type of response, either partial or
complete (HR = 3.9). In conclusion, Melphalan could be a promising
first-line option for MMM patients with clinical or haematological
symptoms requiring treatment.
4
UI - 11849214
AU - Wang JC; Chen W; Nallusamy S; Chen C; Novetsky AD
TI -
Hypermethylation of the P15INK4b and P16INK4a in agnogenic myeloid
metaplasia (AMM) and AMM in leukaemic transformation.
SO - Br J Haematol 2002 Mar;116(3):582-6
AD - Division of Medical Oncology and Hematology, Brookdale University
Hospital and Medical Center, Brooklyn, NY, USA. JCWANG5@aol.com
Hypermethylation of p15 and p16 genes was determined in 32 patients with
agnogenic myeloid metaplasia(AMM), also known as idiopathic
myelofibrosis (MF). These included 10 patients in leukaemic
transformation phase. Using polymerase chain reaction-based methylation
analysis assay methods, with substantiation using Southern blot
analysis, the study showed no hypermethylation of p15 or p16 genes in
the chronic phase of AMM, but p15 gene hypermethylation was found in
four patients (40%) and p16 gene hypermethylation in two patients (20%)
when they were in leukaemic transformation stage. Furthermore, two of
the patients in leukaemic transformation were found to have both p15 and
p16 gene hypermethylation, demonstrating possible multiple gene
hypermethylation in the same patient. Thus, hypomethylation agents for
treating patients with AMM in leukaemic transformation may be
appropriate for future trials.
5
UI - 11849220
AU - Ishiguro A; Suzuki Y; Mito M; Shimbo T; Matsubara K; Kato T; Miyazaki H
TI -
Elevation of serum thrombopoietin precedes thrombocytosis in acute
infections.
SO - Br J Haematol 2002 Mar;116(3):612-8
AD - Department of Paediatrics, Mizonokuchi Hospital, Teikyo University
School of Medicine, Kawasaki, Japan. ishiguro@med.teikyo-u.ac.jp
To clarify the mechanisms underlying thrombocytosis secondary to
infections, we longitudinally studied serum levels of thrombopoietin
(TPO) and interleukin (IL)-6 in 15 infants and young children with
prominent thrombocytosis (platelets >700 x 10(9)/l) following acute
infections and 116 age-matched controls using an enzyme-linked
immunosorbent assay. The subjects included nine patients with bacterial
infections, three with viral infections and three with non-determined
pathogens. TPO values in the controls were 2.24 +/- 0.87 fmol/ml (mean
+/- SD) with a 95% reference interval of 0.85-4.47 fmol/ml. In the first
week of infection, platelet counts were normal, but TPO values increased
(approximately 10.73 fmol/ml). TPO levels peaked on day 4 +/- 2 at 6.44
+/- 2.37 fmol/ml and then fell gradually. When platelet counts peaked in
the second and third weeks, TPO levels were similar to the controls.
IL-6 levels in the first week rose and dropped more rapidly than TPO.
Serum TPO values were significantly correlated with C-reactive protein
levels (r = 0.688, P < 0.001) and IL-6 levels (r = 0.481, P = 0.027).
These results suggest that TPO contributes to thrombocytosis following
infections in conjunction with IL-6, arguing for additional regulatory
mechanisms of blood TPO levels.
6
UI - 11823051
AU - Datta NS; Long MW
TI -
Modulation of MDM2/p53 and cyclin-activating kinase during the
megakaryocyte differentiation of human erythroleukemia cells.
SO - Exp Hematol 2002 Feb;30(2):158-65
AD - Department of Pediatrics and the Comprehensive Cancer Center, University
of Michigan, Ann Arbor, MI, USA.
OBJECTIVE: This study was undertaken to address the involvement of CDK
activating kinase (CAK), p53, and MDM2 proteins in the mitotic arrest
associated with the acquisition of a polyploid DNA content during
megakaryocyte differentiation of human erythroleukemia (HEL) cells.
METHODS: To evaluate this mechanism we investigated HEL cells as a model
system in which there is a marked increase in DNA content during
megakaryocyte differentiation induced by phorbol-diesters. Specific
cell-cycle phases were separated by centrifugal elutriation and SDS PAGE
and Western analysis were performed to determine the relative abundance
of these proteins. Kinase assays were carried out following
immunoprecipitation of cellular lysates with the antibodies to the
proteins. RESULTS: Polyploid HEL cells show an increase in the abundance
of the CAK complex proteins, CDK7 and cyclin H, and a sixfold increase
in CAK-specific activity. Increased CAK activity in polyploid HEL cells
follows both the downregulation of p53 protein and its decreased
association with CAK complex. Consistent with the reduction of p53,
polyploid HEL cells undergo a dramatic increase in MDM2 protein
abundance that in turn facilitates increased interaction of this protein
with p53. CONCLUSION: These observations demonstrate that deregulated
expression of MDM2 and p53 during megakaryocyte differentiation allow a
relaxation of the control over genomic stability, allowing further
replicative rounds of DNA synthesis.
7
UI - 11836165
AU - Domingo-Claros A; Larriba I; Rozman M; Irriguible D; Vallespi T; Aventin
TI -
A; Ayats R; Milla F; Sole F; Florensa L; Gallart M; Tuset E; Lopez C;
Woessner S
Acute erythroid neoplastic proliferations. A biological study based on
62 patients.
SO - Haematologica 2002 Feb;87(2):148-53
AD - Ciudad Sanitaria y Universitaria de Bellvitge, L'Hospitalet del
Llobregat 08907, Barcelona, Spain. alicia@domingo.com
BACKGROUND AND OBJECTIVES: The terms acute erythroleukemia and AML-M6
are defined in the FAB classification as proliferations of dysplastic
erythroid elements mixed with blasts of myeloid origin, but pure
erythroid leukemias are not included. The recent WHO classification has
a category of acute myeloid leukemia not otherwise categorized, which
includes acute erythroid leukemia (M6) of two subtypes:
M6a-erythroleukemia (erythroid/myeloid) and M6b-pure erythroid leukemia.
The aims of this co-operative study were to discover the incidences of
these different subtypes, and pay special attention to the morphology of
these entities. DESIGN AND METHODS: We reviewed a series of 62 patients
with erythroid neoplastic proliferations. Previous medical history, age,
sex, peripheral blood and bone marrow cell counts, cytochemical stains,
immunophenotype, and cytogenetics were evaluated at presentation. We
analyzed the incidence of erythrocyte, leukocyte and platelet
abnormalities in the peripheral blood. In bone marrow we analyzed
dysplastic features of erythroblasts, granulocytic elements and the
megakaryocytic lineage. RESULTS: Fifty-three patients met the criteria
of M6a subtype of the WHO classification, and 2 were classified as
having pure erythremia (M6b); 7 cases could not be classified according
to the WHO criteria. Fifty-five patients presented with de novo acute
leukemia, and seven patients had secondary acute leukemia. The most
frequent dysplastic features in blood smears were: schistocytes,
tear-drop and pincered cells in erythrocytes; hypogranulation and
hyposegmentation in leukocytes; gigantism and hypogranulation in
platelets. In bone marrow, megaloblastic changes, multinuclearity,
karyorrhexis and basophilic stippling in erythroblasts; hypogranulation
and gigantism in granulocytic series, and micromegakaryocytes and
unconnected nuclei in megakarocytes were the most dysplastic features. A
positive PAS reaction and increase of bone marrow iron with ring
sideroblasts were common features. Trilineage dysplasia was present in
54% of cases. Dysplastic features in granulocytic elements were absent
in 26% of patients and minimal erythroblastic dysplasia was observed in
seven patients. A complex karyotype was seen in 27% of patients;
chromosomes 5 and 7 were the most frequently involved. INTERPRETATION
AND CONCLUSIONS: De novo acute erythroid leukemia was more frequent than
secondary cases in our series. The most frequent type of acute erythroid
proliferation was the WHO M6a subtype and the least the pure erythroid
leukemia. We found a group of seven patients (11%) who could not be
classified according to the WHO criteria. Morphologic findings of
erythrocytes in peripheral blood, such as schistocytes, tear-drop and
pincered cells, were outstanding features. Morphologic aspects remain
one of the most important tools for diagnosing these entities.
8
UI - 9345019
AU - Najean Y; Rain JD
TI -
Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in
292 patients under the age of 65 years.
SO - Blood 1997 Nov 1;90(9):3370-7
AD - Department of Nuclear Medicine, Hopital Saint-Louis, Paris, France.
Nonradiomimetic drugs, hydroxyurea (HU) and pipobroman (Pi), were
administred to relatively young subjects with polycythemia vera (PV) in
an attempt to decrease the leukemogenic risk observed in patients
treated with 32P. Clinical safety, hematological efficacy, risk of
carcinoma or leukemia, and frequency of progression to myelofibrosis
have not yet been defined in long-term studies, and no comparative
studies of HU and Pi have been conducted. Since 1980, 292 patients with
PV diagnosed before the age of 65 years were randomized to receive
treatment with HU (25 mg/kg/d, followed by low-dose maintenance) or Pi
(1.2 mg/kg/d, followed by low-dose maintenance). Patients were followed
and buccal aphthous ulcers (with HU) and gastric pain and diarrhea (with
Pi) sometimes required treatment change, mainly in the HU arm.
Hematological stability, especially in terms of platelet count, was very
often insufficient with HU (45% of cases), but the risk of
thrombo-embolic event was similar in both arms. Actuarial survival was
similar in the two arms and shorter than that of the reference
population. The risk of leukemia was approximately 10% at the 13th year,
with no significant difference between the two arms. The risk of
carcinoma (when excluding the skin cancers) was similar in both groups.
There was a high risk of progression to myelofibrosis in the patients
treated by HU, which was significantly higher than with Pi.
9
UI - 9427717
AU - Sterkers Y; Preudhomme C; Lai JL; Demory JL; Caulier MT; Wattel E;
TI -
Bordessoule D; Bauters F; Fenaux P
Acute myeloid leukemia and myelodysplastic syndromes following essential
thrombocythemia treated with hydroxyurea: high proportion of cases with
17p deletion.
SO - Blood 1998 Jan 15;91(2):616-22
AD - Service des Maladies du Sang, CHU Lille, France.
Treatment with alkylating agents or radiophosphorous (32P) has been
shown to carry a certain leukemogenic risk in myeloproliferative
disorders (MPDs), including essential thrombocytemia (ET). The
leukemogenic risk associated to treatment with hydroxyurea in ET, on the
other hand, is generally considered to be relatively low. Between 1970
and 1991, we diagnosed ET in 357 patients, who were monitored until
1996. One or several therapeutic agents had been administered to 326
patients, including hydroxyurea (HU) in 251 (as only treatment in 201),
pipobroman in 43, busulfan in 41, and 32P in 40. With a median follow-up
duration of 98 months, 17 patients (4.5%) had progressed to acute
myeloid leukemia (AML; six cases) or myelodysplastic syndrome (MDS; 11
cases). Fourteen of these patients had received HU, as sole treatment in
seven cases, and preceded or followed by other treatment in seven cases,
mainly pipobroman (five cases). The remaining three leukemic
progressions occurred in patients treated with 32P (two cases) and
busulfan (one case). The incidence of AML and MDS after treatment, using
32P alone and 32P with other agents, busulfan alone and with other
agents, HU alone and with others agents, and pipobroman alone and with
other agents was 7% and 9%, 3% and 17%, 3.5% and 14%, and 0% and 16%,
respectively. Thirteen of 17 patients who progressed to AML or MDS had
successful cytogenetic analysis. Seven of them had rearrangements of
chromosome 17 (unbalanced translocation, partial or complete deletion,
isochromosome 17q) that resulted in 17p deletion. They also had a
typical form of dysgranulopoiesis combining pseudo Pelger Huet
hypolobulation and vacuoles in neutrophils, and p53 mutation, as
previously described in AML and MDS with 17p deletion. Those seven
patients had all received HU, as the only therapeutic agent in three,
and followed by pipobroman in three. The three patients who had received
no HU and progressed to AML or MDS had no 17p deletion. A review of the
literature found cytogenetic analysis in 35 cases of AML and MDS
occurring after ET, 11 of whom had been treated with HU alone. Five of
35 patients had rearrangements that resulted in 17p deletion. Four of
them had been treated with HU alone. These results show that treatment
with HU alone is associated with a leukemic risk of approximately 3.5%.
A high proportion of AML and MDS occurring in ET treated with HU (alone
or possibly followed by pipobroman) have morphologic, cytogenetic, and
molecular characteristics of the 17p- syndrome. These findings suggest
that widespread and prolonged use of HU in ET may have to be
reconsidered in some situations, such as asymptomatic ET.
10
UI - 11815715
AU - Di Raimondo F; Palumbo GA; Molica S; Giustolisi R
TI -
Angiogenesis in chronic myeloproliferative diseases.
SO - Acta Haematol 2001;106(4):177-83
AD - Institute of Hematology, University of Catania, Azienda Ospedaliera
Pugliese-Ciaccio, Catanzaro, Italy. diraimon@sirio-oncology.it
Increased angiogenic activity has been demonstrated in myelofibrosis
with myeloid metaplasia (MMM), chronic myeloid leukemia (CML), and
essential thrombocythemia (ET) by both bone marrow microvessel density
evaluation and measurement of circulating angiogenic factors. MMM is
probably the disease with the more pronounced angiogenesis among
myeloproliferative disorders but the significance of this finding
remains speculative since the angiogenic activity is not correlated with
any of the clinical and laboratory features of the disease. Circulating
serum levels of angiogenic factors such as vascular endothelial growth
factor (VEGF) and hepatocyte growth factor (HGF) were found increased in
MMM, CML and ET but the frequent thrombocytosis that accompanies these
diseases could limit the interpretation of these data since platelets
and megakaryocytes may be considered a major source at least for VEGF.
However, CML patients treated with interferon were found to have lower
VEGF and HGF levels than untreated or hydroxyurea-treated patients, thus
suggesting a possible antiangiogenic mechanism of this drug. In
addition, preliminary experiences with the antiangiogenic drug
thalidomide have shown therapeutic activity in some myeloproliferative
disorders. Copyright 2001 S. Karger AG, Basel
11
UI - 10997967
AU - Finazzi G; Ruggeri M; Rodeghiero F; Barbui T
TI -
Second malignancies in patients with essential thrombocythaemia treated
with busulphan and hydroxyurea: long-term follow-up of a randomized
clinical trial.
SO - Br J Haematol 2000 Sep;110(3):577-83
AD - Divisions of Haematology, Ospedali Riuniti, Bergamo, and Ospedale S.
Bortolo, Vicenza, Italy.
We have previously demonstrated that hydroxyurea (HU) reduces the rate
of vascular complications in patients with essential thrombocythaemia
(ET) at high risk of thrombosis. However, the relatively short follow-up
(median 27 months) did not enable the evaluation of the risk of
developing secondary malignancies. In this study, we report the
long-term outcome of the 114 patients included in the trial: 56 patients
randomized to receive HU and 58 patients to receive no cytoreductive
therapy. Before randomization, 15 patients had been treated with
busulphan. During the observation period, 29 patients (50%) shifted from
the control to the HU group mainly because of thrombosis. Median
follow-up was 73 months (range 3-94). Analysis was by intention to treat
and, when indicated, by treatment. When analysed by intention to treat,
46 out of 54 patients (85%) originally randomized in the HU group are
alive, compared with 49 of 58 patients (84%) in the control group [not
significant (n.s.)]. Five patients (9%) in the HU group and 26 patients
(45%) in the control group had thrombosis (P < 0.0001). Seven patients
(13%) in the HU group developed secondary acute leukaemia,
myelodysplastic syndromes or solid tumours, compared with only one of
the control group patients (1.7%) (P = 0.032). The occurrence of
secondary malignancies was also analysed by treatment: none of the 20
patients who had never been treated with chemotherapy developed
neoplasia vs. three of the 77 patients given HU only (3.9% n.s.) and
five of the 15 patients given busulphan plus HU (33% P < 0. 0001). This
study showed that: (a) HU reduced the risk of thrombosis in ET patients;
(b) the sequential use of busulphan and HU significantly increased the
risk of second malignancies; and (c) overall survival was not affected
by HU therapy.
12
UI - 11891801
AU - Musolino C; Calabro' L; Bellomo G; Martello F; Loteta B; Pezzano C;
TI -
Rizzo V; Alonci A
Soluble angiogenic factors: implications for chronic myeloproliferative
disorders.
SO - Am J Hematol 2002 Mar;69(3):159-63
AD - Division of Hematology, University of Messina, Italy.
camilla.si@tiscalinet.it
The role of angiogenesis for the progressive growth and metastatic
process of tumours is well established. What is not clear, though, is
the clinical prognostic significance of the angiogenic factors in
malignant haematological diseases. In this study, we have assessed the
plasma and serum levels of two major angiogenic factors, vascular
endothelial growth factor (VEGF) and basic fibroblast growth factor
(b-FGF) in 55 patients affected by chronic myeloproliferative disorders
(CMD). This series included 25 patients with essential thrombocythemia
(ET), 10 patients with chronic myelocytic leukaemia (CML), 14 patients
with polycythemia vera (PV), and 6 patients with primary myelofibrosis
(MF), and they were compared to 20 healthy control subjects. In all
patients the plasma VEGF concentration was significantly increased to
the healthy control group (P < 0.004). The highest concentrations were
found in the patients with ET (178.25 +/- 125.22 pg/ml). The VEGF levels
were significantly higher in CMD patients with vascular complications
than those in CMD patients without complications (P < 0.01). The b-FGF
serum levels also appeared to be significantly higher in almost all the
CMD patients compared to the control group (P < 0.07). A significant
correlation was found between the VEGF levels and the platelet count in
the ET patients and the spleen index in the CML patients. VEGF level, in
this study, is associated with increased risk of thrombotic
complications. There is evidence of increased levels of soluble
angiogenic factors in malignant haematological disorders, but their
contribution to the progression of diseases is yet unclear.
13
UI - 11886385
AU - Damaj G; Delabesse E; Le Bihan C; Asnafi V; Rachid M; Lefrere F;
TI -
Radford-Weiss I; Macintyre E; Hermine O; Varet B
Typical essential thrombocythaemia does not express bcr-abelson fusion
transcript.
SO - Br J Haematol 2002 Mar;116(4):812-6
AD - Service d'Hematologie, Service d'Hematologie Biologique, Departement de
Biostatistique et d'Informatique Medicale, and Laboratoire de
Cytogenetique, Hopital Necker Enfants-Malades, Paris, France.
damajg@marseille.fnclcc.fr
Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder
(MPD) characterized by an elevated platelet count and no identifiable
underlying primary cause. According to the diagnostic criteria of the
Polycythemia Vera Study Group (PVSG), ET lacks features diagnostic for
other MPDs, including the Philadelphia chromosome (Ph) or bcr-abl
rearrangement. Recently, some authors have reported bcr-abl transcript
positivity in ET patients, but these findings remain controversial. The
aim of this study was to investigate whether the bcr-abl transcript
could be found in ET patients and to verify the hypothesis of a new ET
variant. ET patients (n = 121) with a median age at diagnosis of 55
years were enrolled. The bcr-abl transcript status was examined by
multiplex reverse transcription-polymerase chain reaction. Only two
cases were positive for bcr-abl, one of which had the Ph at diagnosis.
The positive bcr-abl transcript was associated, in both cases, with mild
basophilia at diagnosis. After a median follow-up of 43 months (0-309
months), two patients in the bcr-abl-negative group developed Ph and
bcr-abl-negative acute myeloid leukaemia (AML). In contrast, one of the
two patients in the bcr-abl-positive group died from AML 13 years after
diagnosis. In conclusion, our data on a large group of patients shows
the rarity of the bcr-abl transcript in well-established ET. However, a
subset of patients with apparent ET and basophilia may express the
transcript and may constitute a novel entity intermediate between
chronic myeloid leukaemia (CML) and typical ET. A prospective study is
warranted in order to define better the clinical and biological
characteristics of bcr-abl-expressing ET.
14
UI - 11886392
AU - Passamonti F; Malabarba L; Orlandi E; Pascutto C; Brusamolino E; Astori
TI -
C; Barate C; Canevari A; Corso A; Bernasconi P; Cazzola M; Lazzarino M
Pipobroman is safe and effective treatment for patients with essential
thrombocythaemia at high risk of thrombosis.
SO - Br J Haematol 2002 Mar;116(4):855-61
AD - Division of Hematology, IRCCS Policlinico San Matteo, University of
Pavia, Pavia, Italy. f.passamonti@smatteo.pv.it
Essential thrombocythaemia (ET) is a disease associated with an elevated
risk of thrombosis. This study evaluated the efficacy and safety of
pipobroman (PB) in the long-term control of ET patients who had, at
diagnosis, one or more of the following currently known risk factors for
thrombosis or haemorrhage (high-risk patients): age > 60 years, history
of thrombosis or haemorrhage, platelets >1000 x 10(9)/l. From 1978 to
2000, with a median follow-up of 10 years, 118 previously untreated
high-risk ET patients (median age 62 years, range 25-82), were treated
with PB at the starting dose of 0.8-1 mg/kg/d. All patients reached a
platelet count <600 x 10(9)/l and 91% achieved a platelet count <400 x
10(9)/l. During follow-up, 13 patients had thrombosis, with a 10-year
cumulative risk of 14%. Acute myeloid leukaemia, myelofibrosis and solid
tumours occurred in three, two and seven patients with a 10-year
cumulative risk of 3%, 2% and 7% respectively. Actuarial survival at 20
years was 64% and the standardized mortality ratio was 1.1 (95% CI:
0.7-1.7), not statistically different from the general population (P =
0.54). Age was associated with a higher risk of death (P = 0.00009) and
thrombosis (P = 0.003). The duration of PB treatment did not correlate
with the occurrence of second malignancies. This study, with a median
follow-up of 10 years, demonstrates that pipobroman is effective and
well tolerated. The low cumulative 10-year risk of thrombosis, leukaemia
and solid tumours indicates that pipobroman is an adequate treatment for
patients with high risk ET.
15
UI - 11886403
AU - Randi ML; Fabris F; Girolami A
TI -
Second malignancies in patients with essential thrombocythaemia.
SO - Br J Haematol 2002 Mar;116(4):923-4
16
UI - 11921281
AU - Sait SN; Qadir MU; Conroy JM; Matsui S; Nowak NJ; Baer MR
TI -
Double minute chromosomes in acute myeloid leukemia and myelodysplastic
syndrome: identification of new amplification regions by fluorescence in
situ hybridization and spectral karyotyping.
SO - Genes Chromosomes Cancer 2002 May;34(1):42-7
AD - Clinical Cytogenetics Laboratory, Roswell Park Cancer Institute,
Buffalo, New York 14263, USA.
Double minute chromosomes (dmin) are small chromatin bodies consisting
of genes amplified in an extrachromosomal location. dmins are uncommon
in hematologic malignancies; they are seen primarily in acute myeloid
leukemia, with amplification of the MYC oncogene or, less frequently,
the MLL transcription factor. Nine patients with hematologic
malignancies with dmin were seen at the Roswell Park Cancer Institute
between 1985 and 2000; eight had acute myeloid leukemia and one a
myelodysplastic syndrome. Fluorescence in situ hybridization (FISH)
demonstrated MYC amplification on dmin in four patients, but MLL
amplification was not seen. Spectral karyotyping showed that the dmin
derived from chromosome 11 in one patient and from chromosome 19 in two
others without MYC or MLL amplification; derivation from these
chromosomes was confirmed by FISH with chromosome paint probes. The dmin
of chromosome 11 origin hybridized to a bacterial artificial chromosome
(BAC) RP11-112M22 that maps to 11q24.3 and is predicted to contain ETS1
and other markers, including D11S11351 and D11S4091. The dmin of
chromosome 19 origin in one patient hybridized to BACs RP11-46I12 and
RP11-110J19; in the other patient, these clones did not hybridize with
the dmin, but were found to be amplified on a marker chromosome that was
derived from chromosome 19 in that patient's cells. These BACs have been
mapped to 19q12-19q13.1 and 19q11-19q13.1, respectively, and are
predicted to contain the markers D19S409 and D19S919 and the gene for
ubiquinol-cytochrome C reductase, Rieske iron-sulfur polypeptide1
(UQCRFS1). dmin originating from chromosome 19 have not been reported
previously in hematologic malignancies. Copyright 2002 Wiley-Liss, Inc.
17
UI - 11843291
AU - Kirito K; Nagashima T; Ozawa K; Komatsu N
TI -
Constitutive activation of Stat1 and Stat3 in primary erythroleukemia
cells.
SO - Int J Hematol 2002 Jan;75(1):51-4
AD - Department of Medicine, Jichi Medical School, Tochigi, Japan.
Signal transducers and activators of transcription (Stat) proteins play
important roles in the regulation of hematopoiesis as downstream
molecules of cytokine signal transduction. Previously, we demonstrated
that Stat1 and Stat3 are activated by erythropoietin (EPO) in a human
EPO-dependent erythroleukemia cell line UT-7/EPO. We report here that
Stat1 and Stat3 are constitutively activated in freshly isolated
erythroleukemia cells. In addition, EPO promoted cell growth of these
cells, accompanied by enhanced activities of Stat1 and Stat3.
Furthermore, mutation in the Statl/Stat3-binding sites of the c-myc gene
promoter clearly blocked its promoter activity in EPO-stimulated primary
erythroleukemia cells. Thus, Stat1 and Stat3 may support cell growth in
part via c-myc gene activation in primary erythroleukemia cells.
18
UI - 11928616
AU - Gotic M; Cvetkovic M; Bozanovic T; Cemerikic V
TI -
[Successful treatment of primary myelofibrosis with thrombocytosis
during pregnancy with alfa-interferon]
SO - Srp Arh Celok Lek 2001 Nov-Dec;129(11-12):304-8
AD - Institute of Haematology, Clinical Centre of Serbia, Belgrade.
Primary myelofibrosis is predominantly a disease of old age, poor
prognosis and no curable treatment. Thrombocytosis was observed in only
12% of patients. To our knowledge, there is only one reported case of a
young woman with primary myelofibrosis who had a term pregnancy [1]. We
report on a 29-year-old woman with thrombocytosis and medical history of
two miscarriages in the last 2 years, the iirst at 30 weeks of gestation
and the second at 27 weeks. Multiple placental infarctions were
observed. She was without symptoms but with moderate splenomegaly 4.5 cm
below left costal margin). The platelet count was 651 x 10(9)/L, WBC 7.2
x 10(9)/L with normal differential formula, and haemoglobin level 12
g/dl. Bone marrow biopsy showed fibrotic phase of primary myelofibrosis,
with hyperplasia of megacaryocytes, decreased numbers of erythroid and
granulocytic cells, and increased amounts of reticulin fibres.
Cyctogenetic examination of the bone marrow showed normal female
caryotype. Increased numbers of progenitors CFU-Mk, CFU-GM and BFU-E
were observed in peripheral blood, and decreased numbers in bone marrow
cultures. As the patient wished to become pregnant, the treatment with
interferon-a (Roferon A) was started at a dose of 3 MU s.c., three times
per week. The platelet count rapidly decreased at a level of 260-370 x
10(9)/L. The pregnancy was diagnosed 5 months later. At the 24 week of
pregnancy, platelet count raised to 690 x 10(9)/l and the dose of
interferon-a was augmented, 3 MU every day, until delivery. Foetal
growth and placental circulation were monitored by serial
ultrasonography. At the end of 34 weeks of pregnancy, it was noted that
placental flow became insufficient, and after foetal lung maturity was
stimulated with dexamethasone, Cesarean section was performed. Male baby
was born, weighting 2000 g, with respiratory distress syndrome. This
complication was successfully treated, and the child is now one year
old, with normal growth and development. The mother is still on therapy
with interferon-a, 3 MU, three times a week, and the last blood count
was as follows: haemoglobin 10.7 g/dl, WBC 6.1 x 10(9)/L and platelet
comt 437 x 10(9)/L. In conclusion, according to the clinical results of
interferon-d in thrombocytosis and experimental studies which showed the
absence of placental transfer of interferon-d, this therapy could be
recommended to women with primary myelofibrosis who wish to have a baby.
19
UI - 11743611
AU - Duarte ME; Carvalho EF; Cruz EA; Lucena SB; Andress DL
TI -
Cytokine accumulation in osteitis fibrosa of renal osteodystrophy.
SO - Braz J Med Biol Res 2002 Jan;35(1):25-9
AD - Programa Avancado de Biologia Celular Aplicado a Medicine (PABCAM),
Hospital Universitario Clementino Fraga Filho, Universidade Federal do
Rio de Janeiro, Rio de Janeiro, RJ, Brasil. eugenia@urbi.com.br
Bone marrow fibrosis occurs in association with a number of pathological
states. Despite the extensive fibrosis that sometimes characterizes
renal osteodystrophy, little is known about the factors that contribute
to marrow accumulation of fibrous tissue. Because circulating cytokines
are elevated in uremia, possibly in response to elevated parathyroid
hormone levels, we have examined bone biopsies from 21 patients with
end-stage renal disease and secondary hyperparathyroidism. Bone sections
were stained with antibodies to human interleukin-1alpha (IL-1alpha),
IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha) and transforming
growth factor-beta (TGF-beta) using an undecalcified plastic embedding
method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-beta was
evident within the fibrotic tissue of the bone marrow while minimal
IL-11 was detected. The extent of cytokine deposition corresponded to
the severity of fibrosis, suggesting their possible involvement in the
local regulation of the fibrotic response. Because immunoreactive
TGF-beta and IL-6 were also detected in osteoblasts and osteocytes, we
conclude that selective cytokine accumulation may have a role in
modulating bone and marrow cell function in parathyroid-mediated uremic
bone disease.
20
UI - 11902730
AU - Arceci RJ
TI -
Down syndrome, transient myeloproliferative syndrome, and leukemia:
bridging development and neoplasia.
SO - J Pediatr Hematol Oncol 2002 Jan;24(1):1
21
UI - 11902733
AU - Gamis AS; Hilden JM
TI -
Transient myeloproliferative disorder, a disorder with too few data and
many unanswered questions: does it contain an important piece of the
puzzle to understanding hematopoiesis and acute myelogenous leukemia?
SO - J Pediatr Hematol Oncol 2002 Jan;24(1):2-5
AD - Children's Mercy Hospital and Clinics, The Cleveland Clinic Foundation,
Kansas City, Missouri, USA.
22
UI - 11902741
AU - Polski JM; Galambos C; Gale GB; Dunphy CH; Evans HL; Batanian JR
TI -
Acute megakaryoblastic leukemia after transient myeloproliferative
disorder with clonal karyotype evolution in a phenotypically normal
neonate.
SO - J Pediatr Hematol Oncol 2002 Jan;24(1):50-4
AD - Department of Pathology, University of South Alabama College of
Medicine, Mobile, USA.
We report a case of transient myeloproliferative disorder (TMD) in a
neonate without features of Down syndrome (DS) with clonal karyotype
evolution, after apparent spontaneous resolution of TMD, but eventually
progressing to acute megakaryoblastic leukemia (AMKL). The patient had
petechiae, thrombocytopenia, and blastemia. Trisomy 21 with a satellited
Y chromosome (Yqs) was found in proliferating blasts. A stimulated
peripheral blood culture confirmed the constitutional origin of the Yqs,
but did not reveal the presence of any trisomic 21 cell. By the age of 3
months, clonal chromosome evolution in the form of an interstitial
deletion of the long-arm of chromosome 13 [del(13)(q13q31)] was detected
along with trisomy 21 in unstimulated bone marrow cultures. However,
remission was achieved without treatment at the age of 4 months. Trisomy
21 and del(13)(q13q31) were not identified in either cytogenetics or
fluorescence in situ hybridization studies at that time. The child was
asymptomatic until the age of 20 months when anemia and thrombocytopenia
prompted a bone marrow biopsy, revealing changes consistent with AMKL.
The remission proceeded by clonal karyotype evolution in a neonate with
TMD demonstrates that clonal karyotype evolution does not indicate an
immediately progressive disease. However, the development of AMKL after
TMD in this case illustrates the increased risk for leukemia in TMD
cases, even without DS. The gradual clonal evolution of the blasts in
our patient suggests that "multiple hits" oncogenesis applies to TMD
progression to acute leukemia.
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