TRANSLATIONAL AND CLINICAL RESEARCH Pim1 Serine/Threonine Kinase Regulates the Number and Functions of Murine Hematopoietic Stem Cells

The genes and pathways that govern the functions and expansion of hematopoietic stem cells (HSC) are not com-pletely understood. In this study, we investigated the roles of serine/threonine Pim kinases in hematopoiesis in mice. We generated PIM1 transgenic mice (Pim1-Tx) overex-pressing human PIM1 driven by vav hematopoietic pro-moter/regulatory elements. Compared to wild-type littermates, Pim1-Tx mice showed enhanced hematopoiesis as demonstrated by increased numbers of Lin2Sca-11 c-Kit1 (LSK) hematopoietic stem/progenitor cells and cob-blestone area forming cells, higher BrdU incorporation in long-term HSC population, and a better ability to reconsti-tute lethally irradiated mice. We then extended our study using Pim12/2, Pim22/2, Pim32/2 single knockout (KO