OVEREXPRESSION OF HOXB3 IN HEMATOPOIETIC-CELLS CAUSES DEFECTIVE LYMPHOID DEVELOPMENT AND PROGRESSIVE MYELOPROLIFERATION

HOXB3 mRNA levels are high in the earliest CD34(+) lineage(-) bone mar row cells and low to undetectable in later CD34(+)/CD34(-) cells. To g ain some insight into the role this gene may play in hematopoiesis, HO XB3 was overexpressed in murine bone marrow cells using retroviral gen e transfer. Thymi of HOXB3 marrow recipients were reduced in size comp ared with control transplant recipients, with a 24-fold decrease in th e absolute number of CD4(+)CD8(+) cells and a 3-fold increase in the n umber of CD4(-)CD8(-) thymocytes that contained a high proportion of g amma delta TCR+ celIs. B cell differentiation was also perturbed in th ese mice, as indicated by the virtual absence of transduced IL-7-respo nsive pre-B clonogenic progenitors. Recipients of HOXB3-transduced cel ls also had elevated numbers of mature granulocyte macrophage colony-f orming cells in their bone marrow and spleen. Together these results s uggest roles for HOXB3 in proliferation and differentiation processes of both early myeloid and lymphoid developmental pathways.