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E-GEOD-54644 - Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]
Released on 3 June 2014, last updated on 7 June 2014
We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [MPN patients] We have performed microarray gene expression analysis in 93 patients with MPNs (28 PV, 47 ET, 18 MF) and 11 age-matched normal donors.
transcription profiling by array
Fatima Al-Shahrour <email@example.com>, Adam J Bass, Benjamin L Ebert, Craig H Mermel, D G Gilliland, Jay Patel, Jean-Philippe Brunel, Jennifer Pretz, Jihae Ahn, Lambert Busque, Martha Wadleigh, Omar Abdel-Wahab, Outi Kilpivaara, Raajit Rampal, Ross Levine, Todd Hricik, Todd R Golub
Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Rampal R, Al-Shahrour F, Abdel-Wahab O, Patel JP, Brunel JP, Mermel CH, Bass AJ, Pretz J, Ahn J, Hricik T, Kilpivaara O, Wadleigh M, Busque L, Gilliland DG, Golub TR, Ebert BL, Levine RL. , PMID:24740812