National Cancer Institute®
Last Modified: January 1, 2002
UI - 11334367
AU - Bitisik O; Yavuz S; Yasasever V; Dalay N
TI - Telomerase activity in patients with chronic myeloid leukemia and lymphoma.
SO - Res Commun Mol Pathol Pharmacol 2000;107(1-2):3-12
AD - Istanbul University, Oncology Institute, Dept. of Basic Oncology.
Telomeres are repeated DNA sequences, positioned at the ends of chromosomes and are essential for the stable maintenance of chromosomes. The telomere length serves as a mitotic clock determining the remaining replicative capacity of the cell. Telomeric sequences are lost during each cell division, leading to a process thought to contribute to senescence and cell death. The enzyme telomerase adds 5'-TTAGGG-3' repeats to the mammalian telomeres and maintains the telomere length. Telomerase is normally inactive in most somatic cells but telomerase activity is observed in malignancies. In this study telomerase activity was analyzed in patients with chronic myeloid leukemia (CML) and lymphoma by PCR and ELISA. This approach combines highly specific amplification of the telomerase-mediated elongation products with nonradioactive detection in a highly sensitive photometric ELISA. The PCR products were also analyzed by Southern blotting. The telomerase-specific PCR products were seperated by electrophoresis and transferred to a nylon membrane with subsequent detection of the biotinylated amplificates. High activity levels were detected in 17 CML ( 34%) patients. On the other hand, no activity was observed in lymphoma patients. An increase in the shorter telomeric bands was observed in CML patients who displayed a high level of telomerase activity. In contrast to the low enzyme activity, evidence of telomeric repeats were also found in some lymphoma patients by Southern blotting. This may indicate that lymphoma cells may make use of different pathways for maintaining the length of their telomeres.
UI - 11410423
AU - Mattei D; Saglio G; Gottardi E; Gallamini A; Mordini N; Bacigalupo A
TI - Persisting molecular remission ten years after donor lymphocyte infusion for hematologic relapse in chronic myeloid leukemia.
SO - Haematologica 2001 May;86(5):545-6
UI - 11471471
AU - Anonymous
TI - New drug targets genetic malfunction in chronic myeloid leukemia.
SO - Am J Health Syst Pharm 2001 Jul 15;58(14):1282
UI - 11499689
AU - Murgo A; Wood KF; Gravell AE; Cheson BD
TI - Clinical trials referral resource. ST1571.
SO - Oncology (Huntingt) 2001 Jul;15(7):881-2, 885-6
AD - National Cancer Institute, USA.
UI - 11504279
AU - Druker BJ
TI - Current treatment approaches for chronic myelogenous leukemia.
SO - Cancer J 2001 Jul-Aug;7 Suppl 1():S14-8
AD - Leukemia Program, Oregon Health Sciences University, Portland 97201, USA.
Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder that progresses through distinct phases characterized by progressive loss of the differentiation of the malignant clone. Over the past 4 decades, it has been established that the Bcr-Abl protein, created as a consequence of a (9:22) chromosomal translocation, is the cause of the disease. Bcr-Abl functions as a constitutively activated tyrosine kinase, and this kinase activity is absolutely required for the transforming function of the Bcr-Abl protein. Thus, a specific inhibitor of the Bcr-Abl tyrosine kinase would be predicted to be an effective and selective therapeutic agent for CML. STI571, an Abl-specific tyrosine kinase inhibitor, has shown remarkable activity in all phases of CML. The clinical features, molecular pathogenesis, and current treatment options of CML are reviewed along with the development of STI571, the phase I clinical results, and the application of this paradigm to other malignancies.
UI - 11571506
AU - Urbano-Ispizua A; Brunet S; Solano C; Moraleda JM; Rovira M; Zuazu J; de
TI - La Rubia J; Bargay J; Caballero D; Diez-Martin JL; Ojeda E; Perez de Oteiza JP; Ferra C; Espigado I; Alegre A; de La Serna J; Torres P; Riu C; Odriozola J; Rozman C; Sierra J; Garcia-Conde J; Montserrat E; Spanish Group of Allo-PBT Allogeneic transplantation of CD34+-selected cells from peripheral blood in patients with myeloid malignancies in early phase: a case control comparison with unmodified peripheral blood transplantation.
SO - Bone Marrow Transplant 2001 Aug;28(4):349-54
AD - Depatment of Hematology, Hospital Clinic, University of Barcelona, Spain.
An allogeneic transplantation of CD34(+)-selected cells from peripheral blood (allo-PBT/CD34(+)) from HLA-identical sibling donors was performed in 50 adult patients with acute myeloid leukemia in first complete remission (AML CR1) (n = 29), myelodysplastic syndrome (MDS) (n = 4), or chronic myeloid leukemia in first chronic phase (CML CP1) (n = 17). Clinical results were compared to a concurrent group of 50 patients transplanted with unmodified peripheral blood progenitor cells (allo-PBT), matched for age, diagnosis, and disease stage. The median follow-up period was 29 months (range 1-69). The actuarial probability of developing acute GVHD clinical grade II to IV was 16% (95%CI: 6-26) for the allo-PBT/CD34(+) group and 41% (95%CI: 29-57) for the allo-PBT group (P = 0.002). The actuarial probability of developing extensive chronic GVHD was 22% (95%CI: 8-36) for the allo-PBT/CD34(+) group and 47% (95%CI: 31-63) for the allo-PBT group (P = 0.02). Recipients of allo-PBT/CD34(+) had less toxicity associated with the transplant and better Karnofsky index at the last follow-up. For AML/MDS patients, the actuarial probability of disease-free survival (DFS) for recipients of allo-PBT/CD34(+) and allo-PBT was 65% (95%CI: 45-85) vs43% (95%CI: 28-58) (P = 0.05), respectively. These data provide a rationale for a randomised trial of allo-PBT/CD34(+) vs allo-PBT in AML/MDS patients in early stage of the disease.
UI - 11550277
AU - Wang YL; Bagg A; Pear W; Nowell PC; Hess JL
TI - Chronic myelogenous leukemia: laboratory diagnosis and monitoring.
SO - Genes Chromosomes Cancer 2001 Oct;32(2):97-111
AD - Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 413b Stellar-Chance Building, 422 Curie Blvd., Philadelphia, PA 19104, USA.
Rapid developments have occurred both in laboratory medicine and in therapeutic interventions for the management of patients with chronic myelogenous leukemia (CML). With a wide array of laboratory tests available, selecting the appropriate test for a specific diagnostic or therapeutic setting has become increasingly difficult. In this review, we first discuss, from the point of view of laboratory medicine, the advantages and disadvantages of several commonly used laboratory assays, including cytogenetics, fluorescence in situ hybridization (FISH), and qualitative and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). We then discuss, from the point of view of clinical care, the test(s) of choice for the most common clinical scenarios, including diagnosis and monitoring of the therapeutic response and minimal residual disease in patients treated with different therapies. The purpose of this review is to help clinicians and laboratory physicians select appropriate tests for the diagnosis and monitoring of CML, with the ultimate goal of improving the cost-effective usage of clinical laboratories and improving patient care. Copyright 2001 Wiley-Liss, Inc.
UI - 11575716
AU - Shah NP; Sawyers CL
TI - Recent success with the tyrosine kinase inhibitor STI-571--lessons for targeted therapy of cancer.
SO - Curr Opin Investig Drugs 2001 Mar;2(3):422-3
AD - Department of Medicine, University of California, Los Angeles 90095-1678, USA.
UI - 11567987
AU - Goldman JM; Druker BJ
TI - Chronic myeloid leukemia: current treatment options.
SO - Blood 2001 Oct 1;98(7):2039-42
AD - Imperial College School of Medicine, London, United Kingdom. firstname.lastname@example.org
The choice of primary treatment for patients with chronic myeloid leukemia (CML) diagnosed in chronic phase has become exceedingly difficult. There is little doubt that allogeneic stem cell transplantation can eradicate the leukemia and that a graft-versus-leukemia effect makes a major contribution to this result; conversely, only a minority of patients are eligible for transplantation, which still carries an appreciable risk for death or protracted illness. For most patients, interferon-alpha (IFN-alpha) prolongs life to some degree in comparison with hydroxyurea, but it is associated with considerable toxicity. The newly introduced tyrosine kinase inhibitor STI571 induces complete hematologic remission in almost all patients and is associated with a very high rate of cytogenetic response; its capacity to prolong life in comparison with IFN-alpha is not yet established. Here are reviewed some factors that predict survival after nontransplantation therapy and after allografting for CML in chronic phase. Two contrasting options are considered for managing the patient with newly diagnosed disease, and it can be concluded that, for now, allogeneic stem cell transplantation soon after diagnosis should continue to be offered as an option for selected patients. Further experience with the use of STI571 as a single agent or in combination with other antileukemic agents may alter the picture in the near future.
UI - 11570925
AU - Dalton SR; Ririe DW; Neuhauser TS
TI - Cauda equina syndrome in a 65-year-old man, status post-bone marrow transplant for chronic myeloid leukemia.
SO - Arch Pathol Lab Med 2001 Oct;125(10):1385-6
AD - Department of Pathology, Wilford Hall Medical Center, Lackland AFB, Texas, USA.
UI - 11579507
AU - Tanaka M; Kanamori H; Kuwabara H; Yamaji S; Kamijo A; Taguchi J; Fujita
TI - H; Fujisawa S; Matsuzaki M; Mohri H; Ishigatsubo Y [Successful second transplant from one-locus HLA-mismatched unrelated donor for graft rejection following initial transplant from another unrelated donor in a patient with chronic myelogenous leukemia]
SO - Rinsho Ketsueki 2001 Aug;42(8):656-8
AD - First Department of Internal Medicine, Yokohama City University School of Medicine.
We report a patient with chronic myelogenous leukemia who received a second transplant from a one-locus HLA-mismatched unrelated donor after rejection of an initial bone marrow graft. For the first transplant, HLAs were fully matched, conditioning with busulfan + cyclophosphamide (CY) was applied, and cyclosporin A + short-term methotrexate (sMTX) was used for prophylaxis against GVHD. A complete chimera was not obtained, and the graft was rejected on day 122. For the second transplant, there was a one-HLA locus (DR) mismatch, conditioning was done with total body irradiation + cytarabine + CY, and GVHD prophylaxis consisted of FK506 + sMTX. Engraftment was obtained on day 27, and no graft failure was occurred at the time of writing. This case suggests that strong immunosuppression may have prevented rejection of the second bone marrow graft.
UI - 11585707
AU - Ullrich O; Grune T
TI - Proteasomal degradation of oxidatively damaged endogenous histones in K562 human leukemic cells.
SO - Free Radic Biol Med 2001 Oct 1;31(7):887-93
AD - Dept. of Cell- and Neurobiology, Institute of Anatomy, Humboldt University Berlin, Schumannstrasse 20/21, D-10098 Berlin, Germany.
A number of antitumor drugs act via the oxidation of nuclear material in the tumor cell. It is therefore important to know if tumor cells can effectively and precisely cope not only with oxidatively induced DNA damage, but also with nuclear protein oxidation. In this study, we investigated the endogenous degradation of oxidatively damaged histones in K562 human leukemic cells after oxidative challenge and demonstrated a link to the overall cellular stress response pathways by poly-ADP-ribose-polymerase (PARP). After an oxidative challenge, endogenous nuclear protein degradation, as well as histone degradation, was enhanced. Among the histone fractions, histone H1 revealed the highest degradation rate, and more than 85% of the total degraded H1 disappeared in the first 30 min after oxidative challenge. Short-term degradation of histones up to 30 min, as well as long-term degradation up to 48 h after oxidative challenge, was significantly reduced in the presence of the PARP inhibitor 3-aminobenzamide, and nearly completely abrogated by the selective proteasome inhibitor lactacystin. Immunoprecipitation experiments indicated that the proteasome specifically degraded oxidized histones. Thus, we show that the nuclear proteosome system in tumor cells is capable of preventing the accumulation of oxidized proteins in this compartment and may suggest further treatment strategies to effectively interfere with the protein "repair" and replacement strategies of tumor cells.
UI - 11601004
AU - Su XY; Cao Q; He KL
TI - [Chromosomal abnormalities in 38 CML cases of various phases]
SO - Zhonghua Yi Xue Za Zhi 1999 Jan;79(1):34-7
AD - Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai 200025.
OBJECTIVE: To study the genomic abnormality underlying the blast crisis of chronic myeloid leukemia(CML). METHODS: 15 CML patients in blast crisis (BC), 3 in accelerated phase (AP) and 20 in chronic phase (CP) were analyzed by conventional cytogentics, comparative genomic hybridization (CGH) and dual color chromosomal painting. RESULTS: Philadelphia (Ph) chromosome was identified in every case studied. Only 5 among 20 CP patients had additional abnormalities while 12 out of 14 patients with disease progression (BC + AP) showed extra numerical and/or structural chromosmal aberrations. Cytogenetically, the most common chromosome gains during BC and AP were double or triple Ph chromosome(5/14), trisomy 8(5/14), trisomy 7(1/14) and 17 (1/14). Three cases showed the same region being involved in translocations t(1;17)(q12-21;q10), t(1;10) (q12-21;q26) and t(1;11)(q12-21;p15). CGH analysis detected genetic imbalances in 8 cases. In one case, a very complex chromosmal translocation del(3), del(6)(q13-21), der(6)t(17;3;6), der(17)t(6;17) was characterized by chromosomal painting. CONCLUSION: We find that the combined use of CGH, chromosomal painting, and classic cytogenetic analysis allows a better evaluation of the genomic aberration involved in CML blastic transformation, and offers new directions for its further molecular investigation.
UI - 11601240
AU - Yao B; Guo M; Pian H
TI - [Cytogenetic analysis and bcr/abl mRNA detection in chronic myeloid leukemia]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Mar;20(3):137-9
AD - Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100039.
OBJECTIVE: To define the relationship between Ph chromosome and BCR/ABL mRNA expression in chronic myeloid leukemia (CML) patients, and compare cytogenetic analysis and PCR method. METHODS: Marrow or peripheral blood samples from 33 CML patients were analyzed by R banding technique and PCR method. Eleven patients who received allogeneic BMT or alpha-IFN + low dose HU were followed up. RESULTS: In 33 patients, 29 were Ph(+), 30 expressed BCR/ABL mRNA. In 6 patients who received BMT, 4 were Ph(-), 2 were Ph(+). However, 2 patients were (-), 4 were (+) by PCR method. In 5 patients who received alpha-IFN, the percentage of Ph(+) cells reduced after 6 and 12 months treatment than before treatment in 2 cases respectively. In 41 samples, 34 cases were consistent by 2 methods. CONCLUSION: Each method, Cytogenetic analysis or PCR has its advantage and defect. The better method are integration of 2 methods in diagnosis and treatment monitoring of CML patients, so that provide real and beneficial information for clinic.
UI - 11489902
AU - Boren J; Cascante M; Marin S; Comin-Anduix B; Centelles JJ; Lim S;
TI - Bassilian S; Ahmed S; Lee WN; Boros LG Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells.
SO - J Biol Chem 2001 Oct 12;276(41):37747-53
AD - Department of Biochemistry and Molecular Biology, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Marti i Franques 1, Barcelona 08028, Spain.
Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13C2]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 microm STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m1/Sigma(m)n ratio in RNA. Based on the in vitro proliferation data, the IC50 of STI571 in K562 cultures is 0.56 microm. The decrease in 13C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m2/Sigma(m)n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.
UI - 11590581
AU - Hamidou MA; Boumalassa A; Larroche C; El Kouri D; Bletry O; Grolleau JY
TI - Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic leukemia.
SO - Semin Arthritis Rheum 2001 Oct;31(2):119-26
AD - Department of Internal Medicine, Hotel-Dieu, University Hospital Nantes, Nantes, France. email@example.com
OBJECTIVE: To determine the clinical aspects of systemic vasculitis associated with chronic myelomonocytic leukemia (CMML). METHODS: In this retrospective study, 8 patients suffering from systemic vasculitis associated with CMML are described. The French and English literature on systemic vasculitis associated with myelodysplasia was reviewed. RESULTS: All 8 patients had a systemic medium-sized vessel vasculitis which fulfilled the American College of Rheumatology criteria for polyarteritis nodosa in the setting of active CMML. Antineutrophil cytoplasmic antibodies (ANCA) were negative in 7 patients. One patient had cytoplasmic ANCA by indirect immunofluorescence without antiproteinase 3 or antimyeloperoxydase antibodies on the enzyme-linked immunosorbent assay. At presentation, 6 patients had fever of unknown origin, 5 had polymyalgia rheumatica, 3 had sensory hearing loss, and 4 had eosinophilia. None had viral infection or drug-associated vasculitis. Diagnostic procedures included renal or hepatic angiography in 6 patients which showed microaneurysms in 4, skin and temporal artery biopsy in 2 which showed vasculitis, and 1 postmortem examination which showed gastroduodenal arteritis. All patients were treated with corticosteroids, and 7 received immunosuppressive drugs. Death was attributable to vasculitis in 2 cases, infection in 3, and other vasculitis-related causes in 2. In a review of the French-English literature, we found 11 similar cases of ANCA-negative systemic vasculitis, generally associated with refractory anemia, with or without blast excess. CONCLUSIONS: Systemic ANCA-negative polyarteritis nodosa-type vasculitis seems closely associated to CMML. Clinical presentation is nonspecific, and systemic vasculitis should be suspected when a patient with myelodysplasia develops atypical manifestations. Renal, gastrointestinal, or hepatic angiography are useful diagnostic procedures when more invasive biopsies should be avoided because of low platelet count. The prognosis of CMML-associated systemic vasculitis is poor. Copyright 2001 by W.B. Saunders Company
UI - 11597734
AU - Marley SB; Davidson RJ; Lewis JL; Nguyen DX; Eades A; Parker S; Goldman
TI - JM; Gordon MY Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo.
SO - Leuk Res 2001 Nov;25(11):997-1002
AD - Leukaemia Research Fund Centre for Adult Leukaemia, Department of Haematology, Imperial College School of Medicine, Hammersmith Campus, DuCane Road, W12 ONN, London, UK.
STI571 targets p210(BCR-ABL) in chronic myeloid leukaemia (CML). In vitro, STI571 reduces self-replication (replating ability) by chronic-phase CML CFU-GM. Here, we studied CFU-GM in advanced-phase (accelerated and blast crisis) CML. The numbers and self-replication of CFU-GM in advanced phase were greater than in the chronic phase. Self-replication by CFU-GM from advanced phase patients was reduced by STI571 or IFN alfa to the same extent as in the chronic phase. The reduced replating ability induced by STI571 correlated with that induced by IFN alpha (r=0.73). STI571 treatment in vivo also reduced replating ability and the numbers of CFU-GM/ml of blood.
UI - 11600728
AU - Bjork J; Albin M; Welinder H; Tinnerberg H; Mauritzson N; Kauppinen T;
TI - Stromberg U; Johansson B; Billstrom R; Mikoczy Z; Ahlgren T; Nilsson PG; Mitelman F; Hagmar L Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?
SO - Occup Environ Med 2001 Nov;58(11):722-7
AD - Department of Occupational and Environmental Medicine, Lund University Hospital, SE-221 85 Lund, Sweden. firstname.lastname@example.org
OBJECTIVES: To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS: A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure-that is, the exposure proportion for each occupational title-was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS: For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS: Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.
UI - 11602316
AU - Carella AM; Melo JV; Goldman JM
TI - Portofino International Conference on Chronic Myeloid Leukemia.
SO - Exp Hematol 2001 Oct;29(10):1147-56
AD - Department of Hematology and Stem Cell Transplantation Unit, Ospedale Casa Sollievo della Sofferenza--IRCCS, San Giovanni Rotondo FG, Italy. email@example.com
UI - 11669299
AU - Hernandez-Boluda JC; Cervantes F; Alvarez A; Costa D; Montserrat E
TI - Single-agent therapy with oral mercaptopurine for nonlymphoid blast crisis of chronic myeloid leukemia.
SO - Ann Hematol 2001 Sep;80(9):516-20
AD - Department of Hematology, Postgraduate School of Hematology Farreras-Valenti, Hospital Clinic, IDIBAPS, University of Barcelona, Spain.
Currently, no effective treatment is available for the nonlymphoid blast crisis (BC) of chronic myeloid leukemia (CML) and because of this the prognosis for such patients remains invariably poor. In an attempt to determine the results provided by palliative treatment with oral 6-mercaptopurine (6-MP) in the above hematological condition, 30 such patients were analyzed for hospital stay, days of intravenous (i.v.) antibiotics, transfusion requirements, response rate, and survival. Thirty patients with nonlymphoid BC matched for their initial characteristics and treated with different i.v. regimens were used for comparison purposes. Patients managed with 6-MP spent less days in hospital (median: 9, range: 0-46 vs median: 42, range: 5-140; P<0.0001), needed antibiotics for less days (median: 0. range: 0-46 vs median: 20, range: 0-57; P<0.0001), and received less platelet transfusions (median: 0, range: 0-20 vs median: 6, range: 0-63; P=0.004) than those treated with i.v. chemotherapy. Although no complete or partial remission was achieved by patients receiving 6-MP vs six in the i.v. chemotherapy group, no significant difference was observed when the survival of both groups was compared (median: 4.7 months, range: 0.1-22.7 vs median: 3.8 months, range: 0.2-12, respectively). These results indicate that 6-MP therapy constitutes a good palliative treatment for patients with nonlymphoid BC of CML. However, new treatment strategies for this hematological condition are required.
UI - 11640869
AU - Chase A; Huntly BJ; Cross NC
TI - Cytogenetics of chronic myeloid leukaemia.
SO - Best Pract Res Clin Haematol 2001 Sep;14(3):553-71
AD - Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts SP2 8BJ, UK.
The standard Philadelphia (Ph) translocation t(9;22), its variants and a proportion of Ph-negative cases are positive for the BCR-ABL fusion gene, as determined by molecular analysis. Extensive deletions of chromosome 9 and 22 derived sequences around the translocation breakpoints on the derivative 9 are seen in 10-30% of patients at diagnosis and may confer a worse prognosis. Additional cytogenetic changes can occur in the few months before or during disease progression and are often specific for blast morphology; however, the molecular basis of the most common additional cytogenetic abnormalities is largely unknown. Cytogenetics is important for monitoring patient response to treatment but is increasingly being replaced by the more sensitive and less invasive techniques of RT-PCR and FISH. Copyright 2001 Harcourt Publishers Ltd.
UI - 11672777
AU - Gonzalez FA; Anguita E; Mora A; Asenjo S; Lopez I; Polo M; Villegas A
TI - Deletion of BCR region 3' in chronic myelogenous leukemia.
SO - Cancer Genet Cytogenet 2001 Oct 1;130(1):68-74
AD - Department of Haematology, Hospital Clinico San Carlos, Madrid, Spain.
The t(9;22)(q34;q11) produces the BCR/ABL fusion gene which codifies a 210 kb protein with a strong tyrosine kinase activity and is involved in cellular development and growth. Because this translocation is a reciprocal event, it could give rise to a second fusion gene, ABL-BCR, on the derivative 9q+. We analyzed the influence of the 3' M-BCR deletion on the clinical picture at diagnosis and disease outcome in 57 patients with a clinical diagnosis of CML. Molecular studies were done on DNA from peripheral blood leukocytes or bone marrow with the restrictions enzymes BglII, EcoRI, HindIII, and BamHI, and the BCR 3' probe (transprobe 1) (Oncogene Science Inc.), which encompasses almost all of the 5.8 Kb of the M-BCR gene area. In 18 patients Southern blot analysis showed deletion of the 3' end of BCR gene (32.7%). There were no significant differences between patients with or without deletion, either in the clinical and laboratory data at the disease diagnosis or at the disease outcome. The absence of differences between the patients with and without 3' BCR deletion supports the hypothesis that the hybrid gene ABL-BCR does not have an important role in leukemogenesis in CML cases.
UI - 11600816
AU - Hochhaus A; Lahaye T; Kreil S; Berger U; Metzgeroth G; Hehlmann R
TI - [Selective inhibition of tyrosine kinases - a new therapeutic principle in oncology]
SO - Onkologie 2001 Sep;24 Suppl 5():65-71
AD - III. Medizinische Klinik, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Mannheim, Germany. firstname.lastname@example.org
Tyrosine kinases are enzymes that regulate mitosis, differentiation, migration, neovascularization, and apoptosis. Their spectrum and association with specific malignancies offer multiple targets for therapeutic intervention. Chronic myelogenous leukemia (CML) represents an ideal target for a therapy using a selective inhibitor of the BCR-ABL tyrosine kinase. The 2-phenylpyrimidine derivative STI571 was rationally designed to inhibit ABL and BCR-ABL tyrosine kinase activities through competitive ATP-binding pocket interactions. Phase II data demonstrate hematologic and cytogenetic responses in interferon refractory chronic-phase, accelerated-phase and blast crisis patients. However, long-term observation is needed to confirm that response data result in prolongation of survival. STI571 is being studied in other malignancies, including leukemias characterized by expression of alternate molecular forms of BCR-ABL and those expressing protein tyrosine kinases with ATP-binding pockets structurally similar to ABL, e.g. c-kit and PDGF-R. Gastrointestinal stromal tumor (GIST) cells overexpress the stem cell factor receptor CD117, the product of the proto-oncogene c-kit. Inhibition of c-kit in vivo results in an immediate metabolic change of the tumor cells, detectable by positron emission tomography. Since c-kit overexpression is inhibited in small-cell lung cancer cell lines, a study with STI571 as second-line therapy of c-kit-positive small-cell lung cancer is in progress. Clinical studies are ongoing in malignancies associated with an enhanced activity of the PDGF-R, such as highgrade glioma, prostate cancer and leukemias with rearrangements of PDGF-R. The development of selective tyrosine kinase inhibitors is considered a promising approach for the design of new drugs. Clinical responses to STI571 in various malignancies may stimulate greater interest in the clinical use of tyrosine kinase inhibitors. Copyright 2001 S. Karger GmbH, Freiburg
UI - 11681414
AU - Yamaguchi H; Inokuchi K; Sakuma Y; Dan K
TI - Mutation of the p51/p63 gene is associated with blastic crisis in chronic myelogenous leukemia.
SO - Leukemia 2001 Nov;15(11):1729-34
AD - Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
The p51/p63 gene, a novel member of the p53 gene family, has recently been identified at 3q27-9. There are at least six major isotypes of p51/p63 mRNA transcripts. p51A/TAp63gamma has the potential to induce apoptosis and growth suppression in a manner similar to p53, and other isotypes may suppress the p53 and p51A1TAp63gamma genes in a dominant-negative manner. We analyzed the mutation and expression of the p51/p63 gene in 80 cases of chronic myelogenous leukemia (CML) to evaluate its role in blastic transformation. Expression of the p51/p63 gene was d