National Cancer Institute®
Last Modified: February 1, 2002
UI - 11464978
AU - Khoury H; Adkins D; Brown R; Pence H; Vij R; Goodnough LT; Westervelt P;
TI - Trinkaus K; Lin HS; DiPersio Y Low incidence of transplantation-related acute complications in patients with chronic myeloid leukemia undergoing allogeneic stem cell transplantation with a low-dose (550 cGy) total body irradiation conditioning regimen.
SO - Biol Blood Marrow Transplant 2001;7(6):352-8
AD - Division of Medical Oncology, Bone Marrow Transplantation and Leukemia Section, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA. email@example.com
Although allogeneic transplantation is a curative therapy for chronic myeloid leukemia (CML), treatment-related mortality is still a major cause of posttransplantation mortality, especially for patients older than 40 years. We investigated, in a phase II trial, the role of a low-dose (550 cGy) high-dose rate (35 cGy/min) single-exposure total body irradiation (TBI) conditioning regimen for allogeneic peripheral blood stem cell (PBSC) transplantation in patients with CML. Between cytokine-mobilized allogeneic PBSC transplantation from HLA-matched siblings following administration of cyclophosphamide (60 mg/kg per day intravenously on days -2 and -1) and single-dose TBI (550 cGy delivered at 30 cGy/min on day 0). Cyclosporine A alone was administered for prophylaxis against graft-versus-host disease (GVHD). Median patient age was 47 years (range, 21-63 years), with 23 patients (77%) older than 40 years. The preparative regimen was well tolerated. Grade 4 toxicities and oral mucositis were not observed. Graft failure did not occur. Severe acute GVHD was observed in 5 patients (17%). The median follow-up was 23 months (range, 6-39 months). Cytogenetic or hematologic relapse was detected in 3 patients (10%), 2 of whom subsequently entered remission following a taper of immunosuppression. Nonrelapse mortality occurred in 5 patients (17%), and the Kaplan-Meier estimate of survival at 2 years was 83% (95% confidence interval, 70%-97%). In summary, this low-dose TBI-based preparative regimen resulted in uniform donor engraftment, with markedly reduced organ toxicity and nonrelapse mortality, in this relatively older cohort of patients with CML.
UI - 11775253
AU - Liu Y; Kleine HD; Engel H; Andreeff M
TI - Cytokine expression of T cells in chronic myeloid leukemia.
SO - Chin Med J (Engl) 2000 Mar;113(3):232-5
AD - Institute of Hematology, People's Hospital, Beijing Medical University, Beijing 100034, China.
OBJECTIVE: To evaluate the function of T cells in chronic myeloid leukemia (CML). METHODS: Interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), and granulocyte macrophage-colony stimulating factor (GM-CSF) gene expressions were investigated by reverse transcription polymerase chain reaction (RT-PCR) assay in fluorescence active cell sorter (FACS) sorted peripheral blood CD2+/CD56-T cells from 12 CML patients, 10 meylodysplastic syndrome (MDS) patients and 7 normal individuals. RESULTS: TNF alpha mRNA was transcribed in T cells from all of the CML, MDS and normal individuals. IL-1 beta mRNA was transcribed in T cells from 10 CML, 9 MDS and 6 normal individuals. Low levels of IL-2 and IL-4 mRNA were detected in 5 CML patients. IL-3, IL-6 and GM-CSF mRNA were undetectable in all samples. CONCLUSION: IL-4 and IL-2 were expressed abnormally in T cells of CML.
UI - 11793598
AU - Schleuning M; Hiddemann W
TI - [New molecular therapy options in hematology and oncology, exemplified by STI571]
SO - Internist (Berl) 2001 Dec;42(12):1591-7
AD - Medizinische Klinik III, Klinikum Grosshadern der Ludwig-Maximilians-Universitat Munchen.
UI - 11792988
AU - Wickenhauser C; Thiele J; Perez F; Varus E; Stoffel MS; Kvasnicka HM;
TI - Beelen DW; Schaefer UW Mixed chimerism of the resident macrophage population after allogeneic bone marrow transplantation for chronic myeloid leukemia.
SO - Transplantation 2002 Jan 15;73(1):104-11
AD - Institute of Pathology, University of Cologne, Joseph-Stelzmannstr. 9, D-50924 Cologne, Germany.
BACKGROUND: Bone marrow macrophages have been recognized to play a crucial role in the functional network that constitutes the microenvironment. In chronic myelogenous leukemia (CML), neoplastic macrophages are presumably responsible for the expansion of the leukemic cell clone. So far, no information is available about a persistence of host-type macrophages after allogeneic bone marrow transplantation (BMT) implicating a lineage-specific mixed chimerism. METHODS: Bone marrow trephine biopsies were investigated in eight male and five female patients with CML after BMT after a sex-mismatched host/donor constellation. Techniques included immunophenotyping (CD68) for identification of resident macrophages and a simultaneous genotyping with X- and Y-chromosome-specific DNA-probes (fluorescence in situ hybridization). Normal bone marrow and specimens of CML patients before BMT served as controls. RESULTS: Contrasting an almost 100% congruence with the genotyping in the controls, a mixed chimerism of the CD68+ macrophages and the other host myeloid cells was found. Until 3 months after BMT, incidence of host-type macrophages ranged from 8% to 10%. This feature was also identifiable in the peculiar subset of pseudo-Gaucher cells (PGCs). The number of host-type macrophages failed to decline significantly during the early posttransplant period, because after almost 4 months these were still detectable. On the other hand, in patients showing an initial-to-manifest leukemic relapse, an insidious conversion of up to 50% from the donor to host-type macrophages and myeloid cells occurred. CONCLUSIONS: The CD68+ resident bone marrow macrophage population including PGCs are involved in the lineage-specific chimerism and minimal residual disease after BMT in CML.
UI - 11697640
AU - Thiele J; Kvasnicka HM
TI - Comparative effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukemia.
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):855-62
AD - Institute of Pathology, University of Cologne, Germany. firstname.lastname@example.org
Therapy-related changes of the bone marrow fiber content remain a controversial issue in hematopathology. This conflict of opinion firstly depends on difficulties to determine the quantity of fibers exactly (semiquantitative grading, morphometry, reference to cellularity). Secondly, the appropriate selection of patients with specific monotherapies including hydroxyurea (HU) and interferon-alpha (IFN) seems to present some problems. Finally, assessment of myelofibrosis is further biased by the different endpoints of sequential examinations. The latter shortcoming can be improved upon by the calculation of the myelofibrosis progression/regression index which describes the ratio between difference of fiber density and observation time. Using strictly defined therapeutic regimens and intervals between sequential trephine biopsies a stimulating effect of IFN administration on bone marrow fibrosis in Ph1+-chronic myelogenous leukemia (CML) has been found. This result is comparable with the failure of this agent to improve myelofibrosis (and splenomegaly) in a considerable number of patients with allied subtypes of chronic myeloproliferative disorders. This is in contrast to the effect HU exerts which is a more fibrolytic or even stabilizing influence on bone marrow fibrosis. This phenomenon is readily demonstrable by the assessment of dynamic features (myelofibrosis progression index). In addition, patients showing a rapid progression of myelofibrosis during IFN and HU treatment of Ph1+-CML are generally associated with a poor risk outcome and a significant worsening of survival.
UI - 11697642
AU - Clark RE; Christmas SE
TI - BCR-ABL fusion peptides and cytotoxic T cells in chronic myeloid leukaemia.
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):871-80
AD - Department of Haematology, University of Liverpool, United Kingdom. email@example.com
The BCR-ABL gene that arises in chronic myeloid leukaemia (CML) is a neoantigen. Peptides derived from the BCR-ABL fusion junction may therefore be immunogenic, if appropriately presented to the immune system. This article reviews data demonstrating that certain junctional peptides will bind to HLA molecules, and that these peptides will elicit specific T-lymphocyte responses in vitro, in both normal subjects and in CML patients. The clinical relevance of these observations is discussed.
UI - 11697648
AU - Kitzis A; Brizard F; Dascalescu C; Chomel JC; Guilhot F; Brizard A
TI - Persistence of transcriptionally silent BCR-ABL rearrangements in chronic myeloid leukemia patients in sustained complete cytogenetic remission.
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):933-44
AD - Laboratoire de Genetique Cellulaire et Moleculaire, UPRES EA 2622, CHU de Poitiers, France. firstname.lastname@example.org
Persistence of BCR-ABL rearrangements was demonstrated by D-FISH technique in chronic myeloid leukemia (CML) patients in complete cytogenetic response (CCR) after allogeneic bone marrow transplantation (BMT) or interferon-alpha therapy (IFN-alpha). Samples from bone marrow aspirate or peripheral blood or both were analyzed by conventional cytogenetics, Southern blot, fluorescent interphase in situ hybridization (FISH), and quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). In all patients, FISH detected 1% to 12% nuclei with a BCR-ABL fusion gene, whereas Q-RT-PCR were negative or weakly positive. Based on these results, we hypothesize that the BCR-ABL genomic rearrangement remains unexpressed in a small percentage of cells whatever the treatment (IFN-alpha or BMT), and this in spite of the negativity of the RT-PCR-based classical molecular remission criterion. These data corroborate those obtained by other investigators and point to the need for follow-up of CML patients in CCR over an extensive period, at the DNA level to evaluate the residual disease and at the RNA level (Q-RT-PCR) to estimate the risk of relapse and guide the therapeutic decision. Experimental models suggesting the persistence of positive BCR-ABL cells are discussed and tentative explanations of tumor "dormancy" are proposed.
UI - 11697649
AU - Vey N; Balatzentko G; Lafage M; Sainty D; Bouabdallah R; Chabannon C;
TI - Blaise D; Gastaut JA; Gabert J Survey of early disapearance of BCR/ABL fusion transcript after allogeneic or autologous stem cell transplantation for chronic myelogenous leukemia.
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):945-52
AD - Department of Hematology, Institut Paoli-Calmettes and Universite de la Mediterranee, Marseille, France. email@example.com
The detection of BCR-ABL specific RNA by RT-PCR has been shown to predict relapse when positive 6 months after allogeneic stem cell transplantation (SCT) for chronic myelogenous leukemia (CML). In the present study, the focus was on evaluation of residual disease during the first weeks following SCT. In this study, 177 blood or marrow samples were obtained from 33 patients who received allogeneic (20 patients) or autologous (13 patients) SCT on day 0, day 30 and every 3 months for 1 year. T-cell depletion (TCD) was performed in 4 cases. On day 0 (day of graft infusion), 10/30 evaluable patients had negative RT-PCR (33%) regardless of pretransplant characteristics. On day 30, 14/18 patients (77%) from the allogeneic group had negative RT-PCR versus 0% in the autologous group. 2/4 patients who received TCD allogeneic grafts had day 30-positive PCR. Five patients in the allogeneic group had at least one positive RT-PCR sample between day 30 and day 90: 3 of them subsequently relapsed suggesting possible correlation between early positivity and relapse. Our results show that disappearance of MRD can be achieved within 3 months after transplantation in the majority of patients treated with allogeneic but not after autologous SCT. This suggests that the GVL effect might be operational early during the first weeks following transplantation.
UI - 10905245
AU - Gunsilius E; Duba HC; Petzer AL; Kahler CM; Grunewald K; Stockhammer G;
TI - Gabl C; Dirnhofer S; Clausen J; Gastl G Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells.
SO - Lancet 2000 May 13;355(9216):1688-91
AD - Division of Haematology and Oncology, University of Innsbruck, Austria. firstname.lastname@example.org
BACKGROUND: Vascular endothelial cells lost from the blood-vessel endothelium through necrosis or apoptosis must be replaced. We investigated in a leukaemia model whether bone-marrow-derived endothelial cells contribute to this maintenance angiogenesis. METHODS: We studied six patients with chronic myelogenous leukaemia (CML) carrying the BCR/ABL fusion gene in their bone-marrow-derived cells. We screened endothelial cells generated in vitro from bone-marrow-derived progenitor cells and vascular endothelium in myocardial tissue for the BCR/ABL fusion gene by in-situ hybridisation. For detection of donor-type endothelial cells after transplantation of haemopoietic stem cells, recipient tissue was stained with monoclonal antibodies against donor-type HLA antigens. FINDINGS: We identified the BCR/ABL fusion gene in variable proportions (0-56%) of endothelial cells generated in vitro. Endothelial cells expressing the fusion gene were found in the vascular endothelium of a patient. In a recipient of an allogeneic stem-cell transplant, normal donor-type endothelial cells were detected in the vascular endothelium. INTERPRETATION: These findings suggest that CML is not solely a haematological disease but originates from a bone-marrow-derived haemangioblastic precursor cell that can give rise to both blood cells and endothelial cells. Moreover, normal bone-marrow-derived endothelial cells can contribute to the maintenance of the blood vascular endothelium. The integration of bone-marrow-derived endothelial cells into the vascular endothelium provides a rationale for developing vascular targeting strategies in vasculopathies, inflammatory diseases, and cancer.
UI - 11734309
AU - Kearney P; Suter M; Biggs JC
TI - Rapid clonal development in a relapsed CML 11 years post replete allogeneic bone marrow transplantation.
SO - Leuk Res 2002 Jan;26(1):111-5
AD - Haematology Department, St Vincent's Hospital Darlinghurst, Darlinghurst, NSW 2010, Sydney, Australia. email@example.com
Long-term survival of chronic myeloid leukaemia (CML) patients transplanted in chronic phase with a replete marrow have been described previously. The same success has not been achieved with patients in more advanced stages of the disease. We describe a CML patient who received an allogeneic bone marrow transplantation in accelerated phase. Cytogenetic and molecular analysis confirmed donor chimaerism, and the absence of the BCR-ABL mRNA. Almost 12 years post-transplant relapse was noted. Cytogenetic analyses showed a complex evolving karyotype. These findings are correlated with the longitudinal molecular analysis utilising real-time and VNTR PCR.
UI - 11734299
AU - Kishino K; Muroi K; Kawano C; Obata T; Sugano N; Nakagi Y; Nagashima T;
TI - Watari K; Iwamoto S; Ozawa K Evaluation of engraftment by ABO genotypic analysis of erythroid burst-forming units after bone marrow transplantation.
SO - Leuk Res 2002 Jan;26(1):13-7
AD - Division of Cell Transplantation and Transfusion, Jichi Medical School, Minamikawachi, 329-0498, Tochigi, Japan.
Six patients received an allogeneic bone marrow transplant from HLA-identical ABO-mismatched donors. ABO genotype of erythroid burst-forming units (BFU-E) from peripheral blood was analyzed using polymerase chain reaction with sequence specific primers (PCR-SSP). After bone marrow transplantation (BMT), engraftment of donor cells by ABO genotypic analysis of BFU-E was compared with ABO phenotypic analysis of red blood cells (RBCs). During the early stage after BMT, ABO genotype of BFU-E in the recipients converted to that of the donors. In contrast, mixed ABO phenotype of RBCs persisted for about 3 months. In one patient, autologous hemopoietic cell recovery was detected by the ABO genotypic analysis before clinical manifestation. ABO genotypic analysis of BFU-E is relevant for enagraftment after ABO-mismatched BMT.
UI - 11734305
AU - Balasubramanian N; Advani SH; Zingde SM
TI - Protein kinase C isoforms in normal and leukemic neutrophils: altered levels in leukemic neutrophils and changes during myeloid maturation in chronic myeloid leukemia.
SO - Leuk Res 2002 Jan;26(1):67-81
AD - Biochemistry and Molecular Biology Division, Cancer Research Institute, Parel, 400012, Mumbai, India.
Protein kinase C (PKC) is reported to play a role in maturation of the myeloid cell and functions of the mature neutrophil. The neutrophils in chronic myeloid leukemia (CML) exhibit defects in several functions. As a step towards understanding the role of PKC in the defects in function of the leukemic cells, this study investigates the expression of PKC isoforms, their subcellular distribution, levels and kinase activity in the normal and leukemic neutrophils. It also investigates changes in representative PKC isoforms during myeloid maturation. This study confirms the presence of PKC alpha, beta and delta and shows, for the first time, the presence of non conventional PKC isoform theta, atypical PKC isoform lambda/iota and PKC isoform mu in normal human neutrophils. In unstimulated cells all the detected PKC isoforms showed a predominantly cytosolic localisation in normal and CML neutrophils. Cytosol-membrane distribution of PKC alpha and delta were significantly altered in leukemic neutrophils as compared to normal cells. Cytosolic levels of all PKC isoforms were reduced in CML neutrophils with PKC alpha, beta, iota, theta, and mu showing a significant decrease. Cytosolic levels of PKC delta contrary to the trend observed for other PKC isoforms showed a slight increase in CML cells, while its membrane levels were significantly reduced in CML neutrophils. Total PKC kinase activity in CML neutrophil cytosol was significantly reduced, while specific kinase activity of two representative isoforms, PKC alpha and delta, from normal and CML neutrophils were similar, thereby increasing the significance of the altered levels of PKC isoforms in CML, and highlighting their role in the defects in function exhibited by the leukemic neutrophils. The levels of PKC delta and iota increased and decreased respectively as the leukemic myeloid cell matured from the blast to the neutrophil, while the levels of PKC alpha and beta were not altered. This suggests a role for PKC delta and iota in the maturation of the leukemic myeloid cell.
UI - 11426572
AU - Carella AM
TI - Mini-ice protocol is better than high-dose hydroxyurea to mobilize Ph-negative cells in earlier phases of chronic myelogenous leukemia.
SO - Leuk Lymphoma 2001 Jan;40(3-4):447-8
UI - 11780326
AU - Fan E; Hu Y; Zhao C
TI - Human stem cell model to study signal transduction and molecular regulation mechanisms in CML.
SO - Chin Med J (Engl) 2001 Jul;114(7):680-4
AD - State Key Lab of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Science, Tianjin 300020, China.
OBJECTIVE: To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. METHODS: We developed a human model of p210BCR/ABL positive CML by transducing normal human umbilical cord blood CD34+ cells with a retroviral vector containing the b3a2 bcr/abl cDNA. We also examined whether this model recreated the cellular phenotype of CML by assessing cell adhesion, cell migration, cell proliferation and cell survival. RESULTS: We found that significantly more myeloid colony forming units grew from p210BCR/ABL expressing cells, adhesion of p210BCR/ABL expressing CD34+ cells to fibronectin was decreased but migration over fibronectin was enhanced compared with mock transduced CD34+ cells. In this model, we showed that the presence of p210BCR/ABL leads to elevated levels of p27kip in p210BCR/ABL expressing CD34+ cells. We also showed that multidrug resistance-1 (MDR-1) Pgp was upregulated in the p210BCR/ABL expressing cells which correlates with the expression of p210BCR/ABL. CONCLUSION: This primary human CML model recreates most of the features of CML and provides a useful tool to study signal transduction and downstream molecular regulation drived by the p210BCR/ABL oncogene in normal CD34+ cells.
UI - 11835339
AU - Nakamura Y; Nakazato H; Sato Y; Furusawa S; Mitani K
TI - Expression of the TEL/EVI1 fusion transcript in a patient with chronic myelogenous leukemia with t(3;12)(q26;p13).
SO - Am J Hematol 2002 Jan;69(1):80-2
AD - Department of Hematology, Dokkyo University School of Medicine, Tochigi, Japan.
The t(3;12)(q26;p13) translocation is a recurrent chromosomal aberration observed in myeloid malignancies. It has been shown that the translocation results in the fusion of the TEL (ETV6) gene at 12p13 and the EV11 gene at 3q26. We report the first case with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) expressing the TEL/EVI1 fusion transcript. A 26-year-old man was initially diagnosed as having the chronic phase of Ph-positive CML. The t(3;12)(q26;p13) emerged 16 months prior to the myeloid blastic crisis. Reverse transcriptase-polymerase chain reaction detected the TEL/EVI1 transcript without the intervening 5' non-coding exon of EVI1, suggesting that inappropriate expression of the EVI1 protein driven by the TEL promotor could play a critical role in progression to the blast crisis of CML. Copyright 2002 Wiley-Liss, Inc.
UI - 11835347
AU - Mubarak AA; Kakil IR; Awidi A; Al-Homsi U; Fawzi Z; Kelta M; Al-Hassan A
TI - Normal outcome of pregnancy in chronic myeloid leukemia treated with interferon-alpha in 1st trimester: report of 3 cases and review of the literature.
SO - Am J Hematol 2002 Feb;69(2):115-8
AD - Hamad Medical Corporation, Department of Medicine, Hematology/Oncology Division, Doha, Qatar.
Three patients with chronic myeloid leukemia (CML) in chronic phase received interferon-alpha during pregnancy, starting from the 1st trimester. No maternal complications were reported. The 3 patients delivered normal looking babies apart from one baby who was found to have transient mild thrombocytopenia. Subsequently these children were followed for 30, 12, and 4 months and all had normal growth and development. Copyright 2002 Wiley-Liss, Inc.
UI - 11683295
AU - Pont V; Miquel FJ; Grau TC; Hernandez F; Sanchez-Carazo JL; Aliaga A
TI - Skin involvement in chronic myelomonocytic leukaemia as a predictor of transformation into acute myeloid leukaemia.
SO - J Eur Acad Dermatol Venereol 2001 May;15(3):260-2
AD - Department of Dermatology, Hospital General Universitario, Valencia, Spain.
We report on the case of a patient with myelodysplastic syndrome (MDS) who presented with leukaemia cutis preceding development of acute myeloid leukaemia. Leukaemic infiltration of the skin should be considered an early manifestation of leukaemic transformation and an indicator of poor prognosis in MDS.
UI - 11801312
AU - Paz-y-Mino C; Burgos R; Morillo SA; Santos JC; Fiallo BF; Leone PE
TI - BCR-ABL rearrangement frequencies in chronic myeloid leukemia and acute lymphoblastic leukemia in Ecuador, South America.
SO - Cancer Genet Cytogenet 2002 Jan 1;132(1):65-7
AD - Laboratorio de Genetica Molecular y Citogenetica Humana, Departamento de Ciencias Biologicas, Pontificia Universidad Catolica del Ecuador, P.O. Box 17-1-2184, Quito, Ecuador. firstname.lastname@example.org
Different BCR-ABL transcript variants occur more or less frequently, according to the leukemia type. We report the frequencies of BCR-ABL transcript variants studied in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) patients in the Ecuadorian population. The frequencies found for CML patients in this study were 94.6% for the b2/a2 rearrangement and 5.4% for the b3/a2 rearrangement; whereas in ALL, all cases (100%) that presented the BCR-ABL rearrangement had the e1/a2 junction. Since our results differ from the frequencies previously reported, we suggest that this may be due to a different genetic background in the population involved in this study when compared to the populations analyzed in prior studies. Furthermore, we recommend a survey of the BCR-ABL transcript variants and their frequencies in different ethnic groups.
UI - 11801317
AU - Qian J; Xue Y; Sun J; Guo Y; Pan J; Wu Y; Wang W; Yao L
TI - Constitutional Robertsonian translocations in (9;22)-positive chronic myelogenous leukemia.
SO - Cancer Genet Cytogenet 2002 Jan 1;132(1):79-80
UI - 11843399
AU - Jain SP; Henry RJ
TI - Haematocolpos following allogenic bone marrow transplantation for chronic myeloid leukaemia.
SO - BJOG 2001 Dec;108(12):1309-10
AD - Department of Obstetrics and Gynaecology, Poole General Hospital, UK.
UI - 11826673
AU - Somers JA; Shamelian SO; Lowenberg B; Ossenkoppele GJ; Cornelissen JJ
TI - [STI571: a new dimension in the treatment of chronic myeloid leukemia]
SO - Ned Tijdschr Geneeskd 2002 Jan 19;146(3):128-32
AD - Erasmus Medisch Centrum-Daniel den Hoed Kliniek, afd. Hematologie, Groene Hilledijk 301, 3075 EA Rotterdam.
Three patients suffering from chronic myelogenous leukaemia (CML), a 36-year-old woman in blast crisis, and a 64-year-old woman and a 60-year-old man in the chronic phase, participated in a clinical trial with STI571, a recently developed tyrosine kinase inhibitor with relative specificity for the BCR-ABL kinase. In all three patients, complete haematologic remission occurred within 2 months of the treatment being initiated. Subsequently the patient in blast crisis underwent allogeneic stem-cell transplantation. For the second patient, who had experienced many side effects with the standard treatment, STI571 led to a better quality of life. The third patient reached complete cytogenetic remission after 3 months of treatment. The development of STI571 is a major breakthrough in the treatment of CML. There are few side effects and the short-term results are excellent in specific patient categories. Further research is needed to establish the eventual role of STI571 in the treatment of CML.
UI - 11853786
AU - Griffin JD
TI - Resistance to targeted therapy in leukaemia.
SO - Lancet 2002 Feb 9;359(9305):458-9
AD - Leukemia Program, Dana-Farber Cancer Institute, Boston, MA 02115, USA. email@example.com
UI - 11856174
AU - Gidali J; Laszlo E; Halm G; Feher I
TI - Blast colony-forming cell binding from CML bone marrow, or blood, on stromal layers pretreated with G-CSF or SCF.
SO - Cell Prolif 2002 Feb;35(1):1-7
AD - National Institute of Haematology and Immunology, Budapest, Hungary. firstname.lastname@example.org
Blast colony-forming cells (CFU-BL) represent a specific subpopulation of special primitive progenitors characterized by colony formation only in close contact with a preformed stromal layer. CFU-BL derived from bone marrow of chronic myeloid leukaemia (CML) patients have been proved to adhere poorly to bone marrow derived stromal layers suggesting that the appearance of progenitors and precursors in the circulation is due to a defective adhesion of these cells to the bone marrow microenvironment. In the present experiments the effect of short-term incubation of preformed normal bone marrow stroma on the adherence of CML derived CFU-BL was studied. For stroma cultures bone marrow cells were cultured in microplates in the presence of hydrocortisone. Cultures were used when stromal layers became confluent and no sign of haemopoiesis could be observed. CFU-BL were studied by panning plastic non-adherent mononuclear (PNAMNC) bone marrow or blood cells. 8.9 +/- 2.4 colonies/103 PNAMNC (six experiments) were formed from normal bone marrow on stromal layers and 4.8 +/- 2.1 colonies/103 PNAMNC (five experiments) from CML bone marrow. Colony formation from normal bone marrow was not increased if stromal layers were incubated with 100 ng/mL granulocyte colony-stimulating factor (G-CSF) or stem cell factor (SCF). Incubation of stroma with G-CSF or SCF, however, increased the colony formation of PNAMNC from CML bone marrow or blood significantly. These findings suggest that local concentration of haemopoietic growth factors at the time of panning may influence the attachment of CML progenitors to the stroma.
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