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PubMed1981

[Chromosome abnormalities associated with Phl and acturial survivorship curve in chronic myeloid leukemia. Probabilistic interpretation of blastic transformation of CML].

Sixty-six patients with chronic myelogenous leukemia, all with Philadelphia chromosome, have been studied for chromosomic abnormalities associated (CAA) to Ph', as well as for actuarial curve of survivorship. Patients dying from another disease were excluded from this study. Frequency of cells with CAA was measured and appeared strongly higher after blastic transformation than during myelocytic state; probability to be a blastic transformation is closely correlated with this frequency. On the other hand, actuarial curve of survivorship is very well represented by an exponential curve. This suggests a constant rate of death during disease evolution, for these patients without intercurrent disease. As a mean survivance after blastic transformation is very shorter than myelocytic duration, a constant rate of blastic transformation could be advanced: it explains possible occurrence of transformation as soon as preclinic state of a chronic myelogenous leukemia. Even if CAA frequency increases after blastic transformation, CAA can occur a long time before it and do not explain it: submicroscopic origin should be searched for the constant rate of blastic transformation would express the risk of a genic transformation at a constant rate during myelocytic state.

Chromosome Aberrations↗
PubMed1995

HIMeg-1, a cell line derived from a CML patient, is capable of monocytic and megakaryocytic differentiation.

We have characterized HIMeg-1, a subclone of the promegakaryoblastic cell line HIMeg, in terms of its capability of proliferation and differentiation when it is exposed to various agents. We observed that phorbol 12-myristate 13-acetate (PMA) arrested HIMeg-1 growth and induced expression of monocytic surface antigens CD11c and CD14, but not the megakaryocytic surface antigen CD14a. In addition, PMA treatment of HIMeg-1 led to rapid activation of mRNA expression of egr-1, a transcription factor involved in regulating differentiation of hematopoietic progenitor cells. On the other hand, treatment of HIMeg-1 with the activated peripheral blood lymphocyte-conditioned medium (PBL-CM) resulted in greatly enhanced incorporation of 3H-thymidine into newly synthesized DNA. This enhanced 3H-thymidine incorporation appears to be specific to HIMeg-1 since the same concentrations of PBL-CM had little effect on the growth of the megakaryoblastic leukemia cell line SAM-1. The PBL-CM-induced DNA synthesis in HIMeg-1 was associated with activation of CD41a and CD41b surface antigen expression and down-regulation of expression of the erythroid marker glycophorin A and the early myeloid surface antigen CD33. HIMeg-1 capable of responding differentially to PMA and PBL-CM by changing its growth rate as well as its differentiation patterns will provide an ideal model to study the underlying mechanism regulating lineage restriction of hematopoietic progenitor cells.

Antigens, CD↗