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Impairment of erythroid and megakaryocytic differentiation by a Leukemia‐Associated and t(9;9)‐derived fusion gene product, SET/TAF‐Iβ‐CAN/Nup214
Author(s) -
Saito Shoko,
Nouno Kaoru,
Shimizu Ritsuko,
Yamamoto Masayuki,
Nagata Kyosuke
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21199
Subject(s) - haematopoiesis , bone marrow , myeloid , biology , leukemia , myeloid leukemia , fusion gene , genetically modified mouse , transgene , gata1 , population , cd34 , cancer research , immunology , microbiology and biotechnology , gene , stem cell , medicine , genetics , environmental health
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. J. Cell. Physiol. 214: 322–333, 2008. © 2007 Wiley‐Liss, Inc.