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Medientyp:
E-Artikel
Titel:
Ott1(Rbm15) Has Pleiotropic Roles in Hematopoietic Development
Beteiligte:
Raffel, Glen D.;
Mercher, Thomas;
Shigematsu, Hirokazu;
Williams, Ifor R.;
Cullen, Dana E.;
Akashi, Koichi;
Bernard, Olivier A.;
Gilliland, D. Gary
Erschienen:
National Academy of Sciences, 2007
Erschienen in:Proceedings of the National Academy of Sciences of the United States of America
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>OTT1(RBM15) was originally described as a 5' translocation partner of the MAL(MKL1) gene in t(1,22)(p13;q13) infant acute megakaryocytic leukemia. OTT1 has no established physiological function, but it shares homology with the spen/Mint/SHARP family of proteins defined by three amino-terminal RNA recognition motifs and a carboxyl-terminal SPOC (Spen paralog and ortholog carboxylterminal) domain believed to act as a transcriptional repressor. To define the role of OTT1 in hematopoiesis and help elucidate the mechanism of t(1,22) acute megakaryocytic leukemia pathogenesis, a conditional allele of Ott1 was generated in mice. Deletion of Ott1 in adult mice caused a loss of peripheral B cells due to a block in pro/pre-B differentiation. There is myeloid and megakaryocytic expansion in spleen and bone marrow, an increase in the Lin⁻Sca-1⁺c-Kit⁺ compartment that includes hematopoietic stem cells, and a shift in progenitor fate toward granulocyte differentiation. These data show a requirement for Ott1 in B lymphopoiesis, and inhibitory roles in the myeloid, megakaryocytic, and progenitor compartments. The ability of Ott1 to affect hematopoietic cell fate and expansion in multiple lineages is a novel attribute for a spen family member and delineates Ott1 from other known effectors of hematopoietic development. It is plausible that dysregulation of Ott1-dependent hematopoietic developmental pathways, in particular those affecting the megakaryocyte lineage, may contribute to OTT1-MAL-mediated leukemogenesis.</p>