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NCI CANCERLIT® Search: Chronic Myelogenous Leukemia - August 2002
National Cancer Institute®
Last Modified: August 1, 2002
- [Study of apoptosis induced by indomethacin in chronic myeloid leukemia]
- [Graft vs. tumor effect in chronic granulocytic leukemia]
- [Study of calcitonin gene methylation in chronic myeloid leukemia by using Hpa II-PCR]
- [Chromosome 8 trisomy in 2 cases of negative ABL/BCR chronic myeloid leukemia ]
- FDA approves Novartis' Gleevec.
- [Occurrence of autoimmune complications in patients with chronic myelocytic leukemia during treatment with interferon alfa]
- Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte
- Disabling Abl-perspectives on Abl kinase regulation and cancer therapeutics.
- [The genetic instability of mismatch repair gene linked microsatellite and the evolution of CML]
- Dose escalation of ara-c may improve response rates in a subgroup of chronic myeloid leukemia patients with poor response to interferon-alpha
- Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.
- Idiopathic intracranial hypertension as the initial manifestation of chronic myeloid leukemia: letter to editor.
- Renal failure associated with a specific inhibitor of BCR-ABL tyrosine kinase, STI 571.
- [STI571 (Glivec)--a new drug for the treatment of chronic myeloid leukemia]
- A case of drug-induced colitis complicating the administration of hydroxycarbamide.
- [ATRA (all-trans retinoic acid) in chronic myeloid leukemia?]
- STI571 (Gleevec) as a paradigm for cancer therapy.
- Cutaneous lesions and chronic myelocytic leukemia (CML) in progression.
- Childbearing and the risk of leukemia in Sweden.
- A complex translocation event between the two homologues of chromosomes 5 leading to a del(5)(q21q33) as a sole aberration in a case clinically
- In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia.
- In vitro effects of STI 571-containing drug combinations on the growth of Philadelphia-positive chronic myelogenous leukemia cells.
- The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA.
- [Successful treatment of chronic myelogenous leukemia with extramedullary megakaryoblastic tumor by allogeneic bone marrow
- Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose.
- Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients: 14 months' experience.
- New prognostic parameters for chronic myelomonocytic leukemia.
Table of Contents
1
UI - 11721434
AU - Tu C; Zhang G; Lu H
TI -
[Study of apoptosis induced by indomethacin in chronic myeloid leukemia]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Jul;20(7):362-5
AD - Laboratory of Molecular Hematology, Division of Hematology, Second
Affiliated Hospital, Hunan Medical University, Changsha 410011.
OBJECTIVE: To explore the effect of indomethacin(IN) on the apoptosis of
chronic myeloid leukemia(CML) cells, and its molecular mechanisms, for
the purpose of screening a new antileukemic agent. METHODS: CML cell
line K562 and fresh bone marrow cells from 6 untreated Ph+ CML patients
were used for in vitro culture study. The effects of IN on cells were
determined by cell morphology, flow cytometry, DNA electrophoresis, and
RT-PCR. RESULTS: 1. IN induced apoptosis of K562 and fresh CML cells and
inhibited the proliferation of K562 cells. 2. A synergic effect of
inducing K562 cell apoptosis was observed when IN combined with Vp16. 3.
IN down-regulated the level of bcl-2 mRNA without changing the level of
bax mRNA in K562 cells. CONCLUSION: IN can induce apoptosis and inhibit
proliferation in CML cells, and increase the sensitivity of CML cells to
Vp16. Down-regulation of bcl-2 mRNA may be one of the mechanisms of CML
cell apoptosis induced by IN.
2
UI - 12053814
AU - Ruiz-Arguelles GJ
TI -
[Graft vs. tumor effect in chronic granulocytic leukemia]
SO - Rev Invest Clin 2002 Mar-Apr;54(2):154-60
AD - Centro de Hematologia y Medicina Interna, Clinica Ruiz de Puebla, Pue.
gruiz1@clinicaruiz.com
3
UI - 12080652
AU - Tan B; Cao P; Qi Z
TI -
[Study of calcitonin gene methylation in chronic myeloid leukemia by
using Hpa II-PCR]
SO - Hunan Yi Ke Da Xue Xue Bao 1999;24(4):371-3
AD - Department of Hematology, Xiangya Hospital, Hunan Medical University,
Changsha 410008.
To investigate the role of calcitonin(CT) gene hypermethylation in the
transformation from the initial chronic phase to blast crisis of chronic
myeloid leukemia, 31 CML patients were studied by using Hpa II-PCR. The
results showed that the 10.52%(2/19) chronic phase, 71.4%(5/7)
accelerated phase and 80.0%(4/5) blast crisis of patients had CT gene
hypermethylation and that the increased methylation of the CT gene were
related with the disease progression. The reports indicated that the
hypermethylation of CT gene might be a useful marker for predicting the
evolution of CML and selecting chronic phase patients for BMT.
4
UI - 12090113
AU - Vargas MT; Fernandez-Novoa Mdel C; Garcia-Creus MD; Gonzalez J
TI -
[Chromosome 8 trisomy in 2 cases of negative ABL/BCR chronic myeloid
leukemia ]
SO - Rev Med Chil 2002 Apr;130(4):460-2
5
UI - 12113126
AU - Anonymous
TI -
FDA approves Novartis' Gleevec.
SO - Expert Rev Anticancer Ther 2001 Jun;1(1):3
6
UI - 12061203
AU - Tothova E; Stecova N; Kafkova A; Fricova M; Svorcova E
TI -
[Occurrence of autoimmune complications in patients with chronic
myelocytic leukemia during treatment with interferon alfa]
SO - Vnitr Lek 2002 May;48(5):380-3
AD - Klinika hematologie LF UPJS a FNsP, Kosice, Slovenska republika.
Several prospective randomized studies have shown that the treatment of
chronic myeloid leukemia with interferon alfa (IFN alpha) prolongs the
survival by comparison with conventional chemotherapy. However,
long-term treatment with Interferon alfa (IFN alpha) can produce or
exacerbate immune-mediated complications (IMC). The purpose of this
study was to analyze the experience with IMC in patients with chronic
myelogenous leukemia (CML) undergoing IFN alpha treatment. PATIENTS AND
METHODS: The occurrence of IMC was evaluated in 76 patients (47 male; 29
female) with Philadelphia chromosome (Ph)-positive CML. The median of
age was 45 years and the duration of disease was 3.9 years. Diagnostic
criteria of IMC were performed in patients with sign and symptoms
suggestive of particular disorders. RESULTS: Well-documented and
clinically evident complications developed in 7 patients after a median
of 19 months (range 1-84) of IFN alpha treatment. These included 9.2%
patients with Ph-positive CML treated with IFN alpha-containing
regimens. Hypothyroidism (H) occurred in 1 patient (1.3%),
immune-mediated hemolysis (HEM) in 2 patients (2.6%) and connective
tissue disorders (CTD) in 4 patients (5.3%) [2-SLE, 1-Raynad's syndrome
and 1-mixed connective tissue syndrome (MCTS)]. IFN alpha was
discontinued in 3 patients and the dose was reduced in 2 patients. Five
of 7 patients (75%) with immune-mediated complications had some degree
of cytogenetic response at the time of the event. The association with
female sex was strong and significant (86% vs 33.6%, x2; 48; p = 0.02).
CONCLUSION: The frequency of IMC of clinical relevance with interferon
alfa therapy in CML increased (long-term therapy). The patients treated
with interferon alfa should be monitored for sign and symptoms of
autoimmunity.
7
UI - 11948108
AU - Saito T; Kanda Y; Kami M; Kato K; Shoji N; Kanai S; Ohnishi T; Kawano Y;
TI -
Nakai K; Ogasawara T; Matsubara H; Makimoto A; Tanosaki R; Tobinai K;
Wakasugi H; Takaue Y; Mineishi S
Therapeutic potential of a reduced-intensity preparative regimen for
allogeneic transplantation with cladribine, busulfan, and antithymocyte
globulin against advanced/refractory acute leukemia/lymphoma.
SO - Clin Cancer Res 2002 Apr;8(4):1014-20
AD - Hematopoietic Stem Cell Transplantation and Hematology Division,
National Cancer Center Hospital, Tokyo 104-0045, Japan.
PURPOSE: Cladribine (2-CdA) is a purine analogue that exhibits activity
against a variety of hematological malignancies and has a potent
immunosuppressive effect. We therefore performed a pilot study to
evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem
cell transplantation (RIST) regimen. EXPERIMENTAL DESIGN: A total of 16
scheduled patients with hematological malignancies were enrolled for
comparison of their data with conventional stem cell transplantation (n
= 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6
days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte
globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases
included acute myelogenous leukemia (n = 6), chronic myelogenous
leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's
lymphoma (n = 2). RESULTS: After RIST, four patients died before day 100
as a result of acute graft-versus-host disease (n = 1), bacteremia (n =
1), disseminated candidasis (n = 1) and congestive heart failure (n =
1). Another patient died of cerebral infarction on day 140. Thus,
acute-phase regimen-related toxicities >grade III were observed in only
one patient. Engraftment and complete donor chimerism were achieved by
day 28 in 14 evaluable patients, and 6 of them (43%) experienced grade
II-IV acute graft-versus-host disease. With a median follow-up of 328
days (range, 231-633 days), the actuarial 1-year overall and
disease-free survival rates were 69% and 50%, respectively. Notably,
among seven high-risk patients (five patients had been in complete
remission two or more times and two not in complete remission with
refractory disease at transplant), only two patients developed leukemia
relapse after RIST. Although the recovery of CD4+ cells was
significantly slower (P = 0.02) in RIST than in conventional stem cell
transplantation, the incidence of clinically documented infections was
not significantly different between the two groups. CONCLUSION: The
results suggest that this novel regimen containing 2-CdA is well
tolerated and induces early complete donor chimerism. The unexpected
durable remission achieved in patients with advanced disease at
transplant suggests the presence of an acceptable antileukemia/lymphoma
effect, which would warrant a further clinical trial.
8
UI - 12086882
AU - Sawyers CL
TI -
Disabling Abl-perspectives on Abl kinase regulation and cancer
therapeutics.
SO - Cancer Cell 2002 Feb;1(1):13-5
AD - Department of Medicine, Molecular Biology Institute, UCLA School of
Medicine, 90095, USA. csawyers@mednet.ucla.edu
Pharmacologic inhibition of the Bcr-Abl tyrosine kinase in human chronic
myeloid leukemia leads to dramatic clinical responses, but relapses
occur in advanced stage patients. New findings about Abl kinase domain
regulation provide insight into novel strategies for targeted therapy.
9
UI - 11798753
AU - Li G; Song Y; Qian L
TI -
[The genetic instability of mismatch repair gene linked microsatellite
and the evolution of CML]
SO - Zhonghua Yi Xue Za Zhi 2000 Mar;80(3):180-2
AD - Institute of Hematology, Chinese Academy of Medical Sciences & Peking
Union Medical College, Tianjin 300020, China.
OBJECTIVE: To explore the relationship between the genetic instability
of microsatellite linked with mismatch repair gene and the evolution of
CML to blast crisis. METHODS: The loss of heterozygosity (LOH) and
microsatellite instability (MSI) of two polymorphic microsatellite
markers, D2s123 and D3s1298, linked with mismatch repair gene hMSH2 and
hMLH1 respectively, were detected by PCR-silver staining method on the
bone marrow cells of 18 CML patients, who clinically progressed from the
chronic phase to accelerated phase or blast crisis. RESULTS: Differences
in microsatellite D2s123 and D3s1298 at the CML accelerated phase or
blast crisis in 5 (27.8%) of the 18 patients were demonstrated compared
with chronic phase. For D2s123, MSI and LOH were observed in 1 of 8
patients with accelerated phase (12.5%) and 2 of 10 patients in blast
crisis (20%). For D3s1298, MSI and LOH were observed in 2 of 10 patients
in blast crisis (20%). CONCLUSION: The genetic alteration of
microsatellite D2s123 and D3s1298 may play a role in the progress of
some CML cases.
10
UI - 11911409
AU - Hilbe W; Kuhr T; Apfelbeck U; Fridrik M; Seewann H; Stoger M; Linkesch
TI -
W; Pont J; Baldinger C; Hartner E; Bernhart M; Geissler D; Krieger O;
Lang A; Lin W; Ludwig H; Duba C; Greil R; Gast G; Thaler J
Dose escalation of ara-c may improve response rates in a subgroup of
chronic myeloid leukemia patients with poor response to interferon-alpha
and low-dose ara-C.
SO - Leuk Lymphoma 2001 Nov-Dec;42(6):1283-8
AD - Department of Internal Medicine, University Hospital, Innsbruck,
Austria.
The present analysis was performed to evaluate the impact of cytosine
arabinoside (ara-C) dose escalation on hematological and cytogenetic
responses in patients with chronic myelogenous leukemia (CML) who failed
to respond to low-dose ara-C (LD ara-C) at a dose of 10 mg/m2/d over 10
days per month and interferon-alpha (IFNalpha, 3.5 MU/d). Following the
same administration schedule, dose escalation of ara-C to 15 and 20
mg/m2/d 1-10 was performed in 36 of 119 patients (30%) due to inadequate
hematological response and/or disease progression. As a result,
improvement of hematological and cytogenetic responses was achieved in
22 (61%) and nine (25%) patients, respectively. Escalated ara-C dose
levels were usually well tolerated, although some patients experienced
deterioration of preexisting side effects. Our results support the
critical role of ara-C dose towards a better disease control in CML.
11
UI - 11870241
AU - Kantarjian H; Sawyers C; Hochhaus A; Guilhot F; Schiffer C;
TI -
Gambacorti-Passerini C; Niederwieser D; Resta D; Capdeville R; Zoellner
U; Talpaz M; Druker B; Goldman J; O'Brien SG; Russell N; Fischer T;
Ottmann O; Cony-Makhoul P; Facon T; Stone R; Miller C; Tallman M; Brown
R; Schuster M; Loughran T; Gratwohl A; Mandelli F; Saglio G; Lazzarino
M; Russo D; Baccarani M; Morra E; The International STI571 CML Study
Group
Hematologic and cytogenetic responses to imatinib mesylate in chronic
myelogenous leukemia.
SO - N Engl J Med 2002 Feb 28;346(9):645-52
AD - M.D. Anderson Cancer Center, Houston, TX 77030, USA.
hkantarj@mdanderson.org
BACKGROUND: Chronic myelogenous leukemia (CML) is caused by the BCR-ABL
tyrosine kinase, the product of the Philadelphia chromosome. Imatinib
mesylate, formerly STI571, is a selective inhibitor of this kinase.
METHODS: A total of 532 patients with late--chronic-phase CML in whom
previous therapy with interferon alfa had failed were treated with 400
mg of oral imatinib daily. Patients were evaluated for cytogenetic and
hematologic responses. Time to progression, survival, and toxic effects
were also evaluated. RESULTS: Imatinib induced major cytogenetic
responses in 60 percent of the 454 patients with confirmed chronic-phase
CML and complete hematologic responses in 95 percent. After a median
follow-up of 18 months, CML had not progressed to the accelerated or
blast phases in an estimated 89 percent of patients, and 95 percent of
the patients were alive. Grade 3 or 4 nonhematologic toxic effects were
infrequent, and hematologic toxic effects were manageable. Only 2
percent of patients discontinued treatment because of drug-related
adverse events, and no treatment-related deaths occurred. CONCLUSIONS:
Imatinib induced high rates of cytogenetic and hematologic responses in
patients with chronic-phase CML in whom previous interferon therapy had
failed.
12
UI - 12134204
AU - Pavithran K; Thomas M
TI -
Idiopathic intracranial hypertension as the initial manifestation of
chronic myeloid leukemia: letter to editor.
SO - Neurol India 2002 Jun;50(2):230
13
UI - 11917072
AU - Kitiyakara C; Atichartakarn V
TI -
Renal failure associated with a specific inhibitor of BCR-ABL tyrosine
kinase, STI 571.
SO - Nephrol Dial Transplant 2002 Apr;17(4):685-7
14
UI - 12082821
AU - Hasselbalch HC
TI -
[STI571 (Glivec)--a new drug for the treatment of chronic myeloid
leukemia]
SO - Ugeskr Laeger 2002 May 27;164(22):2914-7
AD - Medicinsk afdeling, Amtssygehuset Roskilde, DK-4000 Roskilde.
Chronic myeloid leukaemia (CML) is characterised by the occurrence of
the Philadelphia (Ph) chromosome (9/22 translocation) and the formation
of a fusion protein--the BCR-ABL transcript with constitutive activation
of the BCR-ABL tyrosine kinase and consequent changes in the
intracellular signal transduction, which is responsible for the
deregulated myeloid cell proliferation. STI571 (signal transduction
inhibition number 571) is a potent and selective inhibitor of the
BCR-ABL tyrosine kinase. In the chronic phase of the disease, normal
peripheral blood values are achieved within the first month of treatment
in the large majority of patients and in many patients also a cytogenic
response within the following months. The results in the advanced phase
are far less favourable, which is explained by the development of
resistance owing to reactivation of the BCR-ABL signal transduction.
Side effects are primarily nausea, vomiting, various rashes, oedema,
most often in the periorbital region, and musculoskeletal symptoms,
including muscle cramps. Perspectives for treatment with STI571 are
described, as are combinations with alpha-interferon and other
cytostatics with a synergistic profile.
15
UI - 12048644
AU - Sadamoto Y; Ueda T; Matsumoto M; Kubokawa M; Ito K; Kubo H; Tanaka M;
TI -
Harada N; Muta K; Nawata H; Takata M; Yao T
A case of drug-induced colitis complicating the administration of
hydroxycarbamide.
SO - Endoscopy 2002 Jun;34(6):511
AD - Dept. of Medicine and Bioregulatory Science, Graduate School of Medical
Sciences, Kyushu University, Fukuoka, Japan.
ysada@intmed3.med.kyushu-u.ac.jp
16
UI - 12132331
AU - Rak K
TI -
[ATRA (all-trans retinoic acid) in chronic myeloid leukemia?]
SO - Orv Hetil 2002 Jun 9;143(23):1449-50; discussion 1450
17
UI - 11927282
AU - Druker BJ
TI -
STI571 (Gleevec) as a paradigm for cancer therapy.
SO - Trends Mol Med 2002;8(4 Suppl):S14-8
AD - Leukemia Center, Oregon Health & Science University Cancer Institute,
L592, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
drukerb@ohsu.edu
STI571 (Gleevec, imatinib mesylate) exemplifies the successful
development of a rationally designed, molecularly targeted therapy for
the treatment of a specific cancer. This article reviews the
identification of Bcr-Abl as a therapeutic target in chronic myelogenous
leukemia and the steps in the development of an agent to inactivate this
abnormality. Issues related to clinical trials of molecularly targeted
agents are discussed, including dose and patient selection and possible
mechanisms of resistance to STI571. Finally, the potential use of STI571
with different tumors and the translation of this paradigm to other
malignancies are explored.
18
UI - 11904748
AU - Paydas S
TI -
Cutaneous lesions and chronic myelocytic leukemia (CML) in progression.
SO - Ann Hematol 2002 Mar;81(3):178
19
UI - 11899117
AU - Ekstrom K; Wuu J; Hsieh CC; Glimelius B; Lambe M
TI -
Childbearing and the risk of leukemia in Sweden.
SO - Cancer Causes Control 2002 Feb;13(1):47-53
AD - Department of Medical Epidemiology, Karolinska Institutet, Stockholm,
Sweden. karin.ekstrom@mep.ki.se
OBJECTIVE: The possible influence of childbearing on the development of
leukemias in females has received little attention, in spite of
consistent findings of lower incidence rates in females than in males. A
nested case-control study was undertaken to explore if parity and age at
first birth affect the risk of developing these malignancies. METHODS:
In a nationwide cohort defined by a population-based Fertility Register,
we identified 356 women with chronic myeloid leukemia (CML), 819 with
acute nonlymphocytic leukemia (ANLL), and 179 with acute lymphocytic
leukemia (ALL). For each case, five age-matched controls were selected.
Odds ratios were estimated by conditional logistic regression analyses.
RESULTS: There was some evidence of weak negative associations between
parity and age at first birth for CML. Compared to nulliparous women
there was a tendency of a temporal risk reduction of CML for the first
10 years following a delivery. The risk of ANLL was slightly lower in
parous compared to nulliparous women. Neither parity nor age at first
birth was related to the risk of ALL. CONCLUSIONS: We conclude that if
pregnancy-related hormonal or immunological factors have an effect on
the development of leukemia, it is minor and confined to the myeloid
types, chiefly CML. Our study gives some support for treating the
leukemias as separate entities based on both cell lineage and form in
future etiologic studies.
20
UI - 12011996
AU - Heller A; Starke H; Trifonov V; Rubtsov N; Wedding U; Loncarevic I;
TI -
Bleck C; Claussen U; Liehr T
A complex translocation event between the two homologues of chromosomes
5 leading to a del(5)(q21q33) as a sole aberration in a case clinically
diagnosed as CML: characterization of the aberration by multicolor
banding.
SO - Int J Oncol 2002 Jun;20(6):1179-81
AD - Institute of Human Genetics and Anthropology, Jena, Germany.
We report on a patient with a clinically diagnosed Philadelphia negative
chronic myelogenous leukemia (CML) with a so far unrecorded complex
translocation event between the two homologue chromosomes 5. At the
GTG-band level the karyotype was normal, apart from an enlarged
chromosome 5 and an extremely shortened second chromosome 5. Both
derivative chromosomes 5 consisted exclusively of #5 derived material as
proven by 24-color FISH. To characterize the complex aberration in more
detail the multicolor banding (MCB) technique using a chromosome 5
specific probe set was applied. Using this DNA-based high resolution
banding procedure, the karyotype could be described as
46,XX,del(5)(pterright curved arrow q12::q33right curved arrow
qter),ins(5)(pterright curved arrow q15::q12right curved arrow
q21::q21right curved arrow qter). In consequence, the aberration leads
to a partial deletion of the long arm of chromosome 5: del(5)(q21q33),
which would not have been identified using conventional banding
techniques or 24-color FISH.
21
UI - 12135670
AU - La Rosee P; Johnson K; O'Dwyer ME; Druker BJ
TI -
In vitro studies of the combination of imatinib mesylate (Gleevec) and
arsenic trioxide (Trisenox) in chronic myelogenous leukemia.
SO - Exp Hematol 2002 Jul;30(7):729-37
AD - Division of Hematology and Medical Oncology, Oregon Health and Science
University, Portland, OR 97201, USA.
OBJECTIVE: The aim of this study was the preclinical evaluation of
imatinib mesylate (Gleevec, formerly STI571) in conjunction with arsenic
trioxide (As2O3, Trisenox) for the treatment of chronic myelogenous
leukemia (CML). MATERIALS AND METHODS: Tetrazolium-based cell line
proliferation assays (MTT assays) were performed to determine the
cytotoxicity of As2O3 alone and in combination with imatinib. Cell lines
tested in this study were Bcr-Abl-expressing cells (K562, MO7p210,
32Dp210) and parental cells (MO7e, 32D). Isobologram analysis was
performed manually and using the median effect method. In vitro
cytotoxicity also was determined in colony-forming assays using CML
patient cells. Western blot analysis was performed to detect Bcr-Abl
protein levels in K562 cells exposed to As2O3 at graded concentrations.
Bcr-Abl protein level kinetics were correlated with cell viability
(trypan blue count) and activated caspase-3 detected by flow cytometry.
RESULTS: We show additive to synergistic cytotoxicity in Bcr-Abl+ cell
lines depending on inhibitory concentrations and cell type. Results
obtained by colony-forming assays confirmed the findings in cell line
proliferation assays. Flow cytometric detection of activated caspase-3
revealed synergistic activity in K562 cells. Treatment of K562 cells
with As2O3 alone led to down-regulation of Bcr-Abl protein within 24
hours, even at low doses. The decline of Bcr-Abl preceded activation of
caspase-3 and the loss of viable cells. CONCLUSIONS: Favorable
cytotoxicity and proapoptotic activity of imatinib in conjunction with
As2O3 and specific down-regulation of Bcr-Abl protein levels by As2O3 in
K562 cells indicate that As2O3 in combination with imatinib might be
useful for circumventing resistance to imatinib monotherapy.
22
UI - 12173333
AU - Scappini B; Onida F; Kantarjian HM; Dong L; Verstovsek S; Keating MJ;
TI -
Beran M
In vitro effects of STI 571-containing drug combinations on the growth
of Philadelphia-positive chronic myelogenous leukemia cells.
SO - Cancer 2002 May 15;94(10):2653-62
AD - Department of Leukemia, University of Texas M.D. Anderson Cancer Center,
Houston, Texas, USA.
BACKGROUND: Chronic myelogenous leukemia (CML) is characterized by a
molecular aberration, a fusion BCR-ABL gene encoding for aberrant
tyrosine kinase activity, which is crucial in the pathogenesis of CML.
In vitro, inhibition of BCR-ABL protein tyrosine kinase activity by a
tyrosine kinase inhibitor, Imatinib mesylate (STI571; formerly
CGP57148B), successfully suppressed proliferation/survival of the
BCR-ABL positive clones. In clinical studies, hematologic and
cytogenetic remissions have been achieved in most patients with chronic
phase CML; in accelerated and blastic phases of CML, STI571 appeared
less effective. In the current study, the authors tested combinations of
STI571 and cytarabine and homoharringtonine (HHT), drugs with documented
activity in CML. METHODS: The single agents and their combinations were
studied for in vitro effect on proliferation of BCR-ABL positive cell
lines KBM5 and KBM7 by 3(4,5-dimethylthiazol-2yl)-2,5
diphenyl-tetrazolium bromide assay and on primary patient-derived
BCR-ABL cells by clonogenic assays. The in vitro additive, synergistic,
or antagonistic effects of cytarabine and HHT with STI571 were then
investigated by computer-assisted analysis using the CalcuSyn software.
RESULTS: STI571 consistently suppressed BCR-ABL positive cell
proliferation with a dose-effect correlation. In the model system used,
STI571/cytarabine and STI571/HHT combinations were more effective in
inhibiting KBM5 and KBM7 cell growth than each drug as single agent.
These results were also verified in primary CML-derived clonogenic cells
in semisolid cultures. CONCLUSIONS: In this experimental system, our
studies documented additive or synergistic effects with STI571 plus
cytarabine or HHT, supporting the future use of STI571 combinations in
clinical trials in patients with Philadelphia chromosome-positive
leukemias.
23
UI - 12023981
AU - Baxter EJ; Hochhaus A; Bolufer P; Reiter A; Fernandez JM; Senent L;
TI -
Cervera J; Moscardo F; Sanz MA; Cross NC
The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to
PDGFRA.
SO - Hum Mol Genet 2002 Jun 1;11(12):1391-7
AD - Wessex Regional Genetics Laboratory, Salisbury District Hospital,
Salisbury SP2 8BJ, UK.
Chronic myeloid leukaemia (CML) is characterized by the presence of the
BCR-ABL fusion gene, usually in association with the t(9;22)(q34;q11)
translocation. We report here the identification and cloning of a rare
variant translocation, t(4;22)(q12;q11), in two patients with a CML-like
myeloproliferative disease (MPD). RT-PCR indicated that both patients
were negative for BCR-ABL, but FISH analysis suggested that the BCR gene
was rearranged. Since other translocations in MPDs frequently involve
tyrosine kinases, we designed a multiplex PCR to search for mRNA fusions
between BCR and three potential partner genes at 4q12: KIT, KDR and
PDGFRA. An unusual inframe BCR-PDGFRA fusion mRNA was identified in both
patients, with either BCR exon 7 or exon 12 fused to short BCR
intron-derived sequences, which were in turn fused to part of PDGFRA
exon 12. Sequencing of the genomic breakpoint junctions showed that the
chromosome 22 breakpoints fell in BCR introns whereas the chromosome 4
breakpoints were within PDGFRA exon 12. This is the first report of a
fusion gene that involves PDGFRA. Our findings indicate that apparently
simple cytogenetic variants of t(9;22) do not always mask a cryptic
BCR-ABL fusion, even when found in association with clinical and
haematological indications of CML.
24
UI - 12082755
AU - Jinnai M; Hishizawa M; Kitawaki T; Imada K; Ishikawa T; Ohno H; Uchiyama
TI -
T; Ohno T
[Successful treatment of chronic myelogenous leukemia with
extramedullary megakaryoblastic tumor by allogeneic bone marrow
transplantation (from an unrelated donor)]
SO - Nippon Naika Gakkai Zasshi 2002 May 10;91(5):1598-600
AD - Department of Hematology and Oncology, Graduate School of Medicine,
Kyoto University, Kyoto.
25
26
27
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
UI - 12091328
AU - Guglielmi C; Arcese W; Dazzi F; Brand R; Bunjes D; Verdonck LF;
TI -
Schattenberg A; Kolb HJ; Ljungman P; Devergie A; Bacigalupo A; Gomez M;
Michallet M; Elmaagacli A; Gratwohl A; Apperley J; Niederwieser D
Donor lymphocyte infusion for relapsed chronic myelogenous leukemia:
prognostic relevance of the initial cell dose.
SO - Blood 2002 Jul 15;100(2):397-405
AD - Universita La Sapienza, Dipartimento di Biotecnologie Cellulari ed
Ematologia, Unita TMO Allogenico Giuseppe Papa, Rome, Italy.
guglielmi@bce.uniroma1.it
Donor lymphocyte infusion (DLI) can produce durable remissions in
patients with chronic myelogenous leukemia (CML) who have a relapse
after an allogeneic stem cell transplantation. However, the best
modality to administer DLI is still unclear. The effect of the initial
cell dose (ICD; ie, mononuclear cells x 10(8)/kg received in the first
instance) on outcome was retrospectively analyzed in 298 of 344 patients
treated with DLI at 51 centers. Patients were classified into 3 groups
according to the ICD: 98 in group A (
UI - 12091333
AU - Braziel RM; Launder TM; Druker BJ; Olson SB; Magenis RE; Mauro MJ;
TI -
Sawyers CL; Paquette RL; O'Dwyer ME
Hematopathologic and cytogenetic findings in imatinib mesylate-treated
chronic myelogenous leukemia patients: 14 months' experience.
SO - Blood 2002 Jul 15;100(2):435-41
AD - Dept of Pathology, Oregon Health Sciences University, Portland, OR
97201, USA. braziel@ohsu.edu
Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete
hematologic responses (CHRs) in chronic myelogenous leukemia (CML)
patients, but the sequence and timing of morphologic and cytogenetic
changes in CML patients during prolonged imatinib mesylate treatment has
not been described. In this report, we document sequential hematologic
and bone marrow findings in 19
interferon-refractory/interferon-intolerant chronic phase CML patients
on imatinib mesylate for at least 14 months. Patients treated at an
effective oral dose (300 to 600 mg per day) were followed with
peripheral blood (PB) counts, marrow examination, and cytogenetic
studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients
achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19
patients developed cytopenias requiring treatment interruption and/or
dose reduction, but all were able to continue in CHR on study. In
contrast to interferon-alfa treatment, imatinib mesylate-treated CML
patients achieved not only CHR but complete morphologic marrow response.
Normalization of marrow lagged behind PB response; however, by 8 months,
all marrows showed normal or reduced cellularity without morphologic
evidence of CML. Eighteen of 19 patients continued in CHR and
morphologic marrow remission at 14 months; 1 patient relapsed with
chronic phase CML. Although hematologic and marrow responses were
uniform, cytogenetic responses were variable. Complete cytogenetic
responses occurred in 6 patients, with 4 also in remission by
fluorescent in situ hybridization and/or
reverse-transcription-polymerase chain reaction. Six of 19 had partial
and 7 of 19 no cytogenetic response. Several patients acquired
additional clonal cytogenetic abnormalities during therapy, a finding
with significant implications for prognosis and laboratory monitoring in
imatinib mesylate-treated CML patients.
UI - 12123232
AU - Germing U; Strupp C; Aivado M; Gattermann N
TI -
New prognostic parameters for chronic myelomonocytic leukemia.
SO - Blood 2002 Jul 15;100(2):731-2; discussion 732-3
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