YBX1 expression and function in early hematopoiesis and leukemic cells.

Hematopoietic transcription factors play a critical role in directing the commitment and differentiation of hematopoietic stem cells along a particular lineage. Y-box protein (YBX1) is a transcription factor which is widely expressed throughout development and is involved in erythroid cell development; however, its role in early hematopoietic differentiation is not known. This study aims to investigate the role of YBX1 expression in early hematopoietic differentiation and leukemia. Here, we show that YBX1 is highly expressed in mouse erythroid myeloid lymphoid-clone 1 (EML), a hematopoietic precursor cell line, but is down-regulated in myeloid progenitors and GM-CSF-treated EML cells during the course of myeloid differentiation. Moreover, we found that lineage(-)/IL-7R(-)/c-kit(+)/Sca1(+) (LKS; enriched fraction of hematopoietic stem cells) and lineage(-)/IL-7R(-)/c-kit(+)/Sca1(-) myeloid progenitor cells showed high level of YBX1 expression as compared to the differentiated cells like granulocytes in mouse bone marrow. Also, YBX1 protein was expressed at high levels in myeloid leukemic cell lines blocked at different stages of myeloid development. We further investigated the role of YBX1 in leukemic cells by knockdown studies and observed that down-regulation of YBX1 expression in K562 leukemic cells inhibited their proliferation ability, induced apoptosis, and differentiation towards megakaryocytic lineage upon arsenic trioxide treatments relative to untreated. Overall, our data indicates that YBX1 is down-regulated during myeloid differentiation and the aberrant YBX1 expression in leukemic cells could be a contributing factor in the development of leukemia by blocking their differentiation. Thus, YBX1 protein could be an excellent molecular target for therapy in myeloproliferative disorders and leukemia.