Enhanced expression of FHL2 leads to abnormal myelopoiesis in vivo

Z Qian, L Mao, AA Fernald, H Yu, R Luo, Y Jiang, J Anastasi, Peter Valk, Ruud Delwel, MM Le Beau

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)

Abstract

FHL2 is a multifunctional LIM domain protein that acts as a transcriptional modulator mediating proliferation and apoptosis in a tissue-specific manner. Upregulation of FHL2 has been detected in a variety of cancers. We demonstrate that upregulation of FHL2 is associated with a subset of acute myeloid leukemia with a characteristic gene-expression signature, and abnormalities of chromosome 5. In mice, expression of endogenous Fhl2 is downregulated coordinately during the differentiation of hematopoietic cells. Upregulation of FHL2 enhances proliferation of myeloid progenitor cells, and serial-replating efficiency of hematopoietic cells in vitro. Chimeric mice with enforced expression of FHL2 in bone marrow cells, are characterized by an expanded pool of myeloid progenitor cells, enhanced granulopoi esis and megakaryocytopoiesis. In addition, enhanced expression of FHL2 promotes cell-cycle entry of myeloid progenitor cells and increases the frequency of apoptosis of bone marrow cells in vivo. These results raise the possibility that deregulation of FHL2 contributes to the development of human myeloid disorders. Leukemia (2009) 23, 1650-1657; doi:10.1038/leu.2009.78; published online 16 April 2009
Original languageUndefined/Unknown
Pages (from-to)1650-1657
Number of pages8
JournalLeukemia
Volume23
Issue number9
DOIs
Publication statusPublished - 2009

Cite this