The concept of preleukemia: clinical and laboratory studies.

Thirty-five years ago, a handful of astute clinical hematologists began to notice that some of their patients with acute nonlymphocytic leukemia had a history of a preceding ill-defined hemopathy. This "preleukemic" hemopathy was increasingly reported anecdotally and through careful retrospective analyses. In more recent prospective studies, this syndrome has been relatively well defined. Indeed, it is widely accepted that there exists a hematopoietic abnormality not recognizable as classical, overt, acute nonlymphocytic leukemia, which, nonetheless, can represent an early phase of leukemia. In this manuscript, the author reviews the original case reports, the initial retrospective studies, and the prospective studies which have clarified some of the clinical and laboratory features of the preleukemic syndrome. The notion that the preleukemic syndrome represents an established neoplastic process will be reviewed with special attention to assessment of clonal hematopoiesis, cytogenetic studies, and clonal evolution. Studies on induced leukemia and preleukemia in experimental animals and humans will be reviewed as will be the semantic issues which have complicated our ability to compare interinstitutional studies. A simple classification scheme of the myelodysplastic syndromes will be presented as will be a framework agenda for future studies on the pathophysiology of these syndromes.