Origin of near-haploidy in malignant hematopoietic cells.

Overview

Hyperdiploidy is common in neoplastic diseases but severe hypodiploidy or near-haploidy is extremely rare. Acute lymphocytic leukemia (ALL) and blast phase of chronic myelocytic leukemia (BC/CML) are the two most common leukemias where metaphases with as low as 23 chromosomes have been reported. Recent studies have indicated that during the course of malignant development, cells undergo numerous changes, however, it is still not known whether malignant transformation proceeds or results from the near-haploid state. Retrospectively, we have examined 100 metaphases with chromosome counts of 23 to 35 in patients with CML who have not yet progressed to the blastic phase, to see whether such metaphases share any common characteristics with published cases. The unusual behavior of chromosomes 8, 17 and the presence of Ph-chromosomes in 85% of the cells are highly unique features in our study. These observations are compatible with those found in BC/CML patients reported earlier. Therefore, it is hypothesized that selective chromosome loss is a gradual phenomenon and one of these near-haploid clones may replace a diploid clone as the dominant component of the population during blast transformation. Several hypotheses are proposed as to the origin of such clones in malignant hematopoietic stem cells.