Clonal diseases of the myeloid stem cell systems.

Abstract

The structure and kinetics of the hematopoietic stem cell compartment have long been the subject of considerable speculation. Based on morphologic observations of normal and abnormal human marrow and of a perturbed system in experimental animals, primarily the rabbit, in 1938, Downey [1] concluded there was a stem cell capable of giving rise to all hematopoietic tissue. He believed this cell in turn gave rise to a lymphoid stem cell and to a myeloid stem cell. The myeloid stem cell could give rise directly to erythroid, megakaryocytic and monocytic cell lines and in turn produced a tertiary stem cell which could generate neutrophils, eosinophils and basophils. With the development of functional assays for clonal cell growth in vivo and in vitro and through the use of chromosome marked clones this suggested structure has proved to be correct in substance although certain minor variations are indicated. Most definitive studies of the structure of the stem cell compartment are in mice [2] but, in general, the data generated in human diseases suggest that the human stem cell structure is the same as that of the mouse. In Fig. 1, one current “best guess” is shown. There seems little doubt that at least 3 concatenated precursor compartments exist for all myeloid cells. Whether there are still more intermediate stages and whether or not most cells forming colonies in vitro are stem cells (i.e. capable of self-replication) remain open question.