THE TEL ETV6 GENE IS REQUIRED SPECIFICALLY FOR HEMATOPOIESIS IN THE BONE-MARROW/

The TEL (translocation-Ets-leukemia or ETV6) locus, which encodes an E ts family transcription factor, is frequently rearranged in human leuk emias of myeloid or lymphoid origins. By gene targeting in mice, we pr eviously showed that TEL-/- mice are embryonic lethal because of a yol k sac angiogenic defect. TEL also appears essential for the survival o f selected neural and mesenchymal populations within the embryo proper . Here, we leave generated mouse chimeras with TEL-/- ES cells to exam ine a possible requirement in adult hematopoiesis. Although not requir ed for the intrinsic proliferation and/or differentiation of adult-typ e hematopoietic Lineages in the yolk sac and fetal liver, TEL function is essential for the establishment of hematapoiesis of all lineages i n the bone marrow. This defect is manifest within the first week of po stnatal life. Our data pinpoint a critical sole for TEL in the normal transition of hematopoietic activity from fetal liver to bone marrow. This might reflect an inability of TEE-/- hematopoietic stem cells or progenitors to migrate or home to the bone marrow or, more likely, the failure of these cells to respond appropriately and/or survive within the bone marrow microenvironment. These data establish TEE as the fir st transcription factor required specifically for hematopoiesis within the bone marrow, as opposed to other sites of hematopoietic activity during development.