Abnormalities of M egakaryocytes in W / W ” M ice

M ICE OF THE W/WV genotype have hereditary macrycytic anemia,’ and they have defective hematopoietic stem cells that do not proliferate and differentiate normally after transplantation.2’3 The anemia can be corrected by transplantation of functional stem cells into W/WV mice, and splenic tissue from W/W mice supports colony formation by transplanted hematopoietic stem cells in irradiated hosts.6 For these reasons, it has been concluded that mice of the W series have a basic defect in the hematopoietic stem cell or its immediate descendants. Origin of human megakaryocytes from a pluripotential stem cell common also to the erythroid and granulocytic cell lines was suggested by the distribution of the Philadelphia chromosome in marrow cells from patients with chronic granulocytic leukemia (CGL).7 Megakaryocyte participation in CGL has long been recognized,8 and intrinsic abnormalities of megakaryocytes are now also well documented. The megakaryocytes ofCGL have been shown to be small in sizet”#{176}’#{176} and of reduced ploidy.’2”3 Acute myeloblastic leukemia has also been thought to be basically a disorder of a pluripotential hematopoietic stem cell, 4 and evidence for megakaryocytic abnormalities in this disorder or its preleukemic phase has also been reported.’5”6”7 These clinical observations indicate that human megakaryocytes, granulocytes, and erythroid cells all derive from a common pluripotential stem cell. Transplantation studies suggest that the same is true in mice,’8 and, specifically, that the stem cell is involved in mega karyocytopoiesis.’9 If the anemia of W/WV mice originates from a defect in this pluripotential stem cell, then it seems curious that these mice do not show overt abnormalities of platelets and granulocytes. Chervenick and Boggs, in fact, found that megakaryocytes and neutrophils were decreased in the marrow of W/WV mice.2#{176} Lewis et al.3 reported that splenic colonies that formed in irradiated recipients