期刊
BLOOD
卷 109, 期 2, 页码 747-755出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-03-011106
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资金
- NCI NIH HHS [T32 CA9054, T32 CA009054] Funding Source: Medline
- NIAID NIH HHS [R01 AI050831, AI50831] Funding Source: Medline
Genes that are strongly repressed after B-cell activation are candidates for being inactivated, mutated, or repressed in B-cell malignancies. Kruppel-like factor 4 (Klf4), a gene down-regulated in activated murine B cells, is expressed at low levels in several types of human B-cell lineage lymphomas and leukemias. The human KLF4 gene has been identified as a tumor suppressor gene in colon and gastric cancer; in concordance with this, overexpression of KLF4 can suppress proliferation in several epithelial cell types. Here we investigate the effects of KLF4 on pro/pre-B-cell transformation by v-Abl and BCR-ABL, oncogenes that cause leukemia in mice and humans. We show that overexpression of KLF4 induces arrest and apoptosis in the G, phase of the cell cycle. KLF4-mediated death, but not cell-cycle arrest, can be rescued by Bcl-X-L overexpression. Transformed pro/pre-B cells expressing KLF4 display increased expression of p21(CIP) and decreased expression of c-Myc and cyclin D2. Tetracycline-inducible expression of KLF4 in B-cell progenitors of transgenic mice blocks transformation by BCR-ABL and depletes leukemic pre-B cells in vivo. Collectively, our work identifies KLF4 as a putative tumor suppressor in B-cell malignancies. (c) 2007 by The American Society of Hematology
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