C/EBPalpha in leukemogenesis: a matter of being in the right place with the right signals.
Leukemia-initiating cells can originate from hematopoietic progenitor cells that have acquired self-renewal capacity upon transformation with leukemic fusion genes. In this issue of Cancer Cell, Kirstetter and colleagues describe a mouse model for the frequent CEBPA mutations in human acute myeloid leukemia that result in the synthesis of only the 30kDa isoform, but not the 42kDa isoform of C/EBPalpha. This mutation uncouples C/EBPalpha's roles in myeloid differentiation and proliferation control. Furthermore, this mutation activates self-renewal in committed myeloid progenitor cells and induces myeloid malignancy with complete penetrance that is sustained by leukemia-initiating cells with a committed myeloid molecular signature.
Castilla
Lucio H
LH
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA. lucio.castilla@umassmed.edu
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; D050505:Mutant Proteins; D020033:Protein Isoforms