HW, MH and TM carried out the immunohistochemistry and managed the Selleckchem KU57788 database of clinical and pathological information and participated in writing the paper. ST and NS critically revised the manuscript and acquired the grant. NS supervised the experiment, acquired the grant and revised the final version. All authors read and approved the final manuscript.”
“Background Three-amino-acid loop extension (TALE) genes click here belong to the homeobox group and are distinguished by the presence of three extra amino acids in the loop binding the first to the second alpha helix
of the homeodomain . TALE proteins include subfamilies MEINOX and PBC. MEINOX is composed of the members MEIS1, MEIS2, the recently described MEIS3, PREP1, and PREP2 in humans [1, 2]. The PBC subfamily contains PBX1, PBX2, PBX3, and PBX4 proteins [3, 4]. Expression of TALE genes has been related with normal development, differentiation, survival, apoptosis, and with the hematopoietic process [5–10]. Indeed, some TALE genes are targets for viral insertion or for chromosome translocations during
leukemogenesis. In this regard, MEIS1 has been characterized as a common proviral integration site in BXH-2 MLN2238 ic50 mice ; in these mice, leukemic tumors that contain a viral integration site at the MEIS1 locus frequently possess an additional co-integration site in some HOX genes , which suggests the required cooperative effect of MEIS and HOX during leukemogenesis.
Over-expression of MEIS1 in CD34+ hematopoietic cells has been related with suppression of differentiation, promotion of proliferation, and self-renewal. Interestingly, high levels of MEIS1 in myeloid progenitors have been shown to regulate the cellular response PLEK2 to some cytokines, favoring self-renewal or differentiation. Moreover, in the murine myeloid cell line 32Dcl3, it has been observed that MEIS1 can block granulocytic differentiation in response to G-CSF . MEIS1 has been also found over-expressed in human leukemic cells . Other TALE proteins that have been also related with normal hematopoiesis and leukemogenesis comprise members of the PBX group. PBX proteins were first identified as HOX cofactors involved in developmental gene regulation [15, 16]. PBX1 plays a role in the development of blood cell populations because hematopoietic stem cells from PBX1-/- embryos have reduced colony-forming activity and are unable to establish multilineage hematopoiesis in competitive reconstitution experiments . PBX-PREP1 complexes are required for the production of normal CD4 and CD8 T-lymphocytes. Furthermore, PBX-MEIS complexes have been implicated in megakaryocyte differentiation, and PBX-PREP complexes have been also connected with the regulation of Interleukin (IL)-10 production in macrophages during the phagocytosis of apoptotic cells .