Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-Iβ-CAN/ Nup214

Shoko Saito, Kaoru Nouno, Ritsuko Shimizu, Masayuki Yamamoto, Kyosuke Nagata

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

SET-CAN associated with the t(9;9) in acute undifferentiated leukemia encodes almost the entire sequence of SET and the C-terminal two-third portion of CAN, including the FG repeat region. To clarify a role(s) of SET-CAN in leukemogenesis, we developed transgenic mice expressing SET-CAN under the control of the Gata1 gene hematopoietic regulatory domain that is active in distinct sets of hematopoietic cells. SET-CAN transgenic mice showed anemia, thrombocytopenia, and splenomegaly. A significant number of transgenic mice started dying after 6 months post-birth, being in good agreement with the fact that red blood cells and platelets decreased. We found that a significant number of c-kit+ myeloid cells appeared in peripheral blood in transgenic mice. Characterization of the bone marrow cells of transgenic mice indicated impairment in hematopoietic differentiation of erythroid, megakaryocytic, and B cell lineages by SET-CAN. Transgenic mice, in particular, exhibited a high population of the c-kit+Sca-1+Lin- fraction in bone marrow cells compared with that of the control littermates. Our results demonstrate that SET-CAN blocks the hematopoietic differentiation program - one of the characteristics of acute myeloid leukemia.

Original languageEnglish
Pages (from-to)322-333
Number of pages12
JournalJournal of Cellular Physiology
Volume214
Issue number2
DOIs
Publication statusPublished - 2008 Feb 1
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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