Delineating MEIS1 cis- regulatory elements active in hematopoietic cells

MEIS1 (Myeloid ecotropic viral integration site 1) is a homeodomain transcription factor that cooperates with Hox family proteins in both normal and leukemic hematopoiesis.1 MEIS1 is highly expressed in hematopoietic stem cells (HSCs), and its level decreases during differentiation but with a relatively higher expression in the megakaryocytic lineage.2, 3 MEIS1 expression is often elevated in leukemia,4 and it is one of the leukemic stem cell (LSC)-related signature genes whose higher expression is correlated with worse prognosis.5 Previous work, including our own, has shown that MEIS1 acts as an important driver for leukemogenesis.1 Elevated expression of MEIS1 with concurrent high expression of HOX can induce rapid-onset AML in murine models.6 Decreased MEIS1 expression via short hairpin RNA-mediated knockdown has been shown to significantly reduce LSC potential.7, 8 Together, these findings point to the importance of tightly regulated expression of MEIS1 for normal hematopoiesis and reveal how its deregulated expression can be a major factor in leukemogenesis.