Chronic Myelogenous Leukemia — New Concepts

Koeffler, H. Phillip; Golde, DW

doi:10.1056/nejm198105143042004

Cited by 223 publications

(30 citation statements)

References 115 publications

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“…This is comparable to the incidence of 0.90 to 1.6 per 100,000 reported from various countries [1]. The median age of our patients at diagnosis was 38 years, and this is lower than the 43 to 45 years reported by Keoffler and Golde [2]. We did not observe any sex predilection.…”

Section: Pattern Of Chronic Myelogenous Leukemia In Western Libyasupporting

confidence: 82%

Pattern of Chronic Myelogenous Leukemia in Western Libya

1990

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Section: Pattern Of Chronic Myelogenous Leukemia In Western Libyasupporting

confidence: 82%

Pattern of Chronic Myelogenous Leukemia in Western Libya

1990

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“…CML myeloid progenitors display normal mitotic indices, normal responses to colony-stimulating factors and do not proliferate faster than their normal counterparts (Stryckmans et al, 1976;Dormer et al, 1980;Koeffler and Golde, 1981;Strife and Clarkson, 1988). Hematopoietic cell population size is also regulated by apoptosis, for example hemopoetic colony stimulating factors suppress apoptosis (Williams, 1991;Greenberg, 1992), and thus the myeloid expansion seen in CML may be due to enhanced cell survival rather than excessive proliferation.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Bcr-Abl in K562 cells restores susceptibility to apoptosis: Characterization of the apoptotic death

et al. 1997

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We examined the susceptibility of a variety of human leukemic cell lines to the induction of apoptosis. K562, a chronic myelogenous leukemic cell line which expresses the bcr-abl fusion gene, was found to be extremely resistant to apoptosis, irrespective of the inducing agent. This resistance can be attributed to the deregulated Abl kinase activity of bcr-abl, as downregulation of its expression using antisense oligodeoxynucleotides targeted to the beginning of the abl sequence in this chimeric gene rendered these cells susceptible to cytotoxic drug-induced apoptosis. Examination of the morphological and biochemical features of apoptosis in K562 cells revealed the typical membrane blebbing and chromatin condensation associated with this form of cell death. In situ TdT-mediated end labeling of the DNA revealed the presence of strand breaks in the treated cells and field inversion gel electrophoresis revealed the presence of large 10 ± 50 kb fragments. However there was an absence of oligonucleosomal DNA fragmentation, whether or not Bcr-Abl was expressed. Thus, while inhibition of expression of Bcr-Abl renders K562 cells susceptible to apoptosis, the absence of oligonucleosomal DNA fragmentation in these cells is independent of the function of this molecule.

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“…Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome, a reciprocal translocation that results in the BCR-ABL fusion gene (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Long-term follow-up of patients with chronic myeloid leukemia having received autologous stem cell transplantation

Hackanson

Waller

2010

Ann Hematol

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Prior to introduction of imatinib mesylate, the median survival of chronic myeloid leukemia (CML) patients was approximately 60 months and the standard treatment with interferonalpha (IFN-α) resulted in major cytogenetic responses of 20-25 %. As an alternative treatment approach besides allogeneic transplantation intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT) was investigated at that time with the rationale of debulking disease burden and mobilisation and transplantation of Philadelphia chromosome-negative (Ph-) stem cells.In the era of tyrosine kinase inhibitors (TKIs) as state-of-the-art therapy for CML, the concept of autoHSCT has attracted only little interest and long-term follow-up and outcome data after autoHSCT in CML patients is scarce. In this long-term analysis, we report on 21 CML patients, mobilized in early chronic phase (ECP) and transplanted with largely Ph-grafts, who received IFNα as maintenance therapy. Imatinib mesylate was administered upon cytogenetic relapse or disease progression while on IFN-α. The 10-year survival was 61% and 11 patients (52%) were alive at a median follow-up of 12.5 years (range 0.3 -13.8) with 8 patients in complete hematologic remission (CHR) and 3 of 8 in major molecular remission (MMR). While all patients in MMR and 2 of 5 patients in CHR received imatinib, it is noteworthy that three patients remaining in CHR only received IFN-α maintenance after autoHSCT.With the limitations of a small patient population, this is the longest follow-up analysis demonstrating that autoHSCT in CML is very efficient to debulk the disease, restore Phnegative hematopoiesis and is able to induce major and sustained molecular responses in the majority of patients with substantial long-term survival rates.

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Chronic Myelogenous Leukemia — New Concepts

Cited by 223 publications

References 115 publications

Pattern of Chronic Myelogenous Leukemia in Western Libya

Pattern of Chronic Myelogenous Leukemia in Western Libya

Downregulation of Bcr-Abl in K562 cells restores susceptibility to apoptosis: Characterization of the apoptotic death

Long-term follow-up of patients with chronic myeloid leukemia having received autologous stem cell transplantation

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