

Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996868/pdf/ukmss-33568.pdf
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Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling |
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Authors | ![]() | |
Published in | Cancer Cell. 2010, vol. 18, no. 5, p. 524-535 | |
Abstract | The JAK2V617F mutation is associated with distinct myeloproliferative neoplasms, including polycythemia vera (PV) and essential thrombocythemia (ET), but it remains unclear how it generates disparate disorders. By comparing clonally-derived mutant and wild-type cells from individual patients, we demonstrate that the transcriptional consequences of JAK2V617F are subtle, and that JAK2V617F-heterozygous erythroid cells from ET and PV patients exhibit differential interferon signaling and STAT1 phosphorylation. Increased STAT1 activity in normal CD34-positive progenitors produces an ET-like phenotype, whereas downregulation of STAT1 activity in JAK2V617F-heterozygous ET progenitors produces a PV-like phenotype. Our results illustrate the power of clonal analysis, indicate that the consequences of JAK2V617F reflect a balance between STAT5 and STAT1 activation and are relevant for other neoplasms associated with signaling pathway mutations. | |
Keywords | Amino Acid Substitution — Cell Culture Techniques — Cell Differentiation/genetics — Cells, Cultured — Cluster Analysis — Down-Regulation — Gene Expression Profiling — Gene Expression Regulation, Neoplastic — Heterozygote — Humans — Interferons/metabolism — Janus Kinase 2/*genetics — Megakaryocytes/pathology — Myeloproliferative Disorders/*genetics — Phenotype — Phosphorylation — Polycythemia Vera/*genetics — STAT1 Transcription Factor/genetics/*metabolism — STAT5 Transcription Factor/genetics/metabolism — Signal Transduction — Thrombocythemia, Essential/*genetics — Transcriptional Activation | |
Identifiers | PMID: 21074499 | |
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![]() ![]() Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996868/pdf/ukmss-33568.pdf |
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Research group | Population Genomics and Genetics of Complex Traits (892) | |
Citation (ISO format) | CHEN, Edwin et al. Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling. In: Cancer Cell, 2010, vol. 18, n° 5, p. 524-535. doi: 10.1016/j.ccr.2010.10.013 https://archive-ouverte.unige.ch/unige:20617 |