STAT5 in B cell development and leukemia.
Early B cell development depends on a network of transcription factors, whereby E2A and EBF1 regulate B cell specification and Pax5 controls B-lineage commitment. In contrast, activation of the transcription factor STAT5 in response to IL-7R signaling promotes cell survival by activating the prosurvival gene Mcl1 and orders immunoglobulin gene rearrangement by repressing Igk recombination in pro-B cells. Subsequently, it cooperates with the pre-B cell receptor to facilitate pre-B cell expansion. STAT5 also plays a key role in the generation of B cell precursor acute lymphoblastic leukemia, whereby the BCR-ABL1 translocation or the collaboration of JAK2 mutations with overexpression of the thymic stromal lymphopoietin receptor CRLF2 results in constitutive STAT5 activation leading to cytokine-independent survival and growth of leukemic cells.
Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
Stephen
S
Malin
Shane
S
McManus
Meinrad
M
Busslinger
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000276:immunology; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D015851:Interleukin-7; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor; D016044:Fusion Proteins, bcr-abl