Evidence for a multistep pathogenesis of chronic myelogenous leukemia.
To study the relationship of the Philadelphia chromosome (Ph1) to the pathogenesis of chronic myelogenous leukemia, multiple B-lymphoid cell lines were established from a patient with Ph1-positive leukemia who was heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase. Both A and B types of enzyme were found in a 1:1 proportion in normal tissues, but 45 of 63 (71%) Ph1-negative B-lymphoid cells lines derived from this patient showed only the single glucose-6-phosphate dehydrogenase (type B) found in the Ph1-positive leukemic clone. Furthermore, 8 of 33 analyzable lines with B-type enzyme had chromosomal aberrations compared to 0 of 14 lines with A-type glucose-6-phosphate dehydrogenase. These results provide evidence for the suggestion that some cells of the abnormal clone do not express the Ph1 abnormality. Thus, acquisition of Ph1 may not be a sufficient cause for the disease. It is possible that at least two steps are involved in the pathogenesis of Ph1-positive chronic myelogenous leukemia, one causing abnormal proliferation of a clone of pluripotent hematopoietic stem cells and the other inducing Ph1 in descendants of these progenitors.
D001402:B-Lymphocytes / Q000166:cytology*; D002460:Cell Line; D002869:Chromosome Aberrations; D002904:Chromosomes, Human, 21-22 and Y; D005954:Glucosephosphate Dehydrogenase / Q000145:classification; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000209:etiology*
D005954:Glucosephosphate Dehydrogenase