Investigation and characterization of the homeobox gene MEIS2 in acute lymphoblastic leukemia

MEIS2 is a member of the homeobox gene family, that are known to play a pivotal role in embryogenesis as well as organogenesis. An overexpression of MEIS2 has been reported for several solid neoplasms as well as acute myeloid leukemia with t(8;21). Information about the role of MEIS2 in acute lymphoblastic leukemia is scarce (ALL). Here, we could show an overexpression of MEIS2 in bone marrow samples of patients with ALL in comparison to healthy controls. Our data suggest that MEIS2 expression in ALL patients is regulated by promotor methylation. Further, we could observe a proliferation inhibition and reduced clonogenic capacity upon lentiviral mediated MEIS2-knockdown in ALL cell lines. We could demonstrate that the effect is not mediated through apoptosis but rather a cell cycle arrest in the G0-phase. Furthermore, MEIS2 knockdown led to differentially expressed genes, which are involved in B- and T-cell activation, EGF-, FGF-, TGF-beta-, VEGF- signaling as well as the RAS-pathway. Altogether, our data suggests a role of MEIS2 in the leukemogenesis of ALL