Preleukemia. Cytogenetic clues in some confusing disorders

A number of disease states are considered "preleukemic" because they carry a significantly increased risk for the subsequent development of frank leukemia. These include a variety of cytopenias, myeloproliferative disorders, and childhood syndromes. Cytogenetic data suggest that these preleukemic disorders may not be qualitatively different from leukemia but simply represent quantitative differences in the degree of selective growth advantage enjoyed by a proliferating abnormal hemic population. Recent chromosome studies have indicated that a) this proliferation is characteristically clonal in both preleukemia and leukemia, apparently resulting from a heritable change in a marrow stem cell that allows it to escape to some degree from normal growth regulation; b) genetic instability in the clone, with additional genetic change, may often underlie clinical progression from the relative indolence of preleukemia or chronic leukemia to an aggressive stage comparable to acute leukemia; and c) certain specific chromosome segments carry genes important in the acquisition of growth advantage by hematopoietic stem cells, and many of these are common to both preleukemia and leukemia. Expansion of hemic clones may also be influenced significantly by alterations in the growth control mechanisms themselves. For instance, in various preleukemic states, preexisting marrow hypoplasia may permit clones with only minimal selective advantage to reach demonstrable size. Chromosome findings may help to establish the diagnosis and prognosis in preleukemic disorders, but additional long-term data are needed.