Ott1(Rbm15) has pleiotropic roles in hematopoietic development

Glen D. Raffel, Thomas Mercher, Hirokazu Shigematsu, Ifor R. Williams, Dana E. Cullen, Koichi Akashi, Olivier A. Bernard, D. Gary Gilliland

Research output: Contribution to journalArticle

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Abstract

OTT1(RBM15) was originally described as a 5′ translocation partner of the MAL(MKL1) gene in t(1,22)(p13;q13) infant acute megakaryocyte 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.

Original languageEnglish
Pages (from-to)6001-6006
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number14
DOIs
Publication statusPublished - Apr 3 2007

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Megakaryocytes
Leukemia, Megakaryoblastic, Acute
Lymphopoiesis
Mentha
Aptitude
Hematopoiesis
Hematopoietic Stem Cells
Granulocytes
Leukemia
B-Lymphocytes
Spleen
Bone Marrow
Alleles
Genes
Proteins
RNA Recognition Motif

All Science Journal Classification (ASJC) codes

  • General

Cite this

Raffel, G. D., Mercher, T., Shigematsu, H., Williams, I. R., Cullen, D. E., Akashi, K., ... Gilliland, D. G. (2007). Ott1(Rbm15) has pleiotropic roles in hematopoietic development. Proceedings of the National Academy of Sciences of the United States of America, 104(14), 6001-6006. https://doi.org/10.1073/pnas.0609041104

Ott1(Rbm15) has pleiotropic roles in hematopoietic development. / Raffel, Glen D.; Mercher, Thomas; Shigematsu, Hirokazu; Williams, Ifor R.; Cullen, Dana E.; Akashi, Koichi; Bernard, Olivier A.; Gilliland, D. Gary.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 14, 03.04.2007, p. 6001-6006.

Research output: Contribution to journalArticle

Raffel, GD, Mercher, T, Shigematsu, H, Williams, IR, Cullen, DE, Akashi, K, Bernard, OA & Gilliland, DG 2007, 'Ott1(Rbm15) has pleiotropic roles in hematopoietic development', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 14, pp. 6001-6006. https://doi.org/10.1073/pnas.0609041104
Raffel, Glen D. ; Mercher, Thomas ; Shigematsu, Hirokazu ; Williams, Ifor R. ; Cullen, Dana E. ; Akashi, Koichi ; Bernard, Olivier A. ; Gilliland, D. Gary. / Ott1(Rbm15) has pleiotropic roles in hematopoietic development. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 14. pp. 6001-6006.
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