CELL-GROWTH IN CHRONIC MYELOID-LEUKEMIA AT BLAST CRISIS

During the stage of blast crisis, the increase in the population of peripheral blasts in one examined untreated CML patient, obeyed an exponential equation of growth that requires a maintained equal proportion of proliferating to quiescent blasts. A model of cell growth at CML blast crisis is presented, which interprets the required constancy of equal-size blast subcompartments in terms of regulation of the G0 --> G1 flow, the latter involving activation of one cell out of three interacting quiescent blasts in contact. This model is discussed in the light of evidence that G0 blast activation involves membrane-bound interacting sites interfering with growth-promoting pathways. The model-predicted proliferative index (f) value of 0.5 +/- 0.16 is found to be nearly identical to a reported estimate of the H-3-thymidine-labeling index of CML blasts at the crisis stage of the disease. It is also close to corresponding indexes of CML blood and marrow progenitor cells and to labeling indexes of AML and ALL large blasts.