Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis
Paper by Raajit K. Rampal indexed on Europe PMC as PubMed record 24740812, in Blood (2014), one of the most cited records naming an author with this name at Memorial Sloan Kettering Cancer Center.
Overview
Genomic studies have identified somatic alterations in the majority of myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the majority of MPN patients and CALR mutations in JAK2-negative MPN patients. However, the role of JAK-STAT pathway activation in different MPNs, and in patients without JAK2 mutations, has not been definitively delineated. We used expression profiling, single nucleotide polymorphism 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 JAK2 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.
Indexed on Europe PMC as PubMed record 24740812 (DOI 10.1182/blood-2014-02-554634). Its author list gives "Rampal R" with the affiliation "Human Oncology and Pathogenesis Program, and Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY;", which names Memorial Sloan Kettering Cancer Center; that is how the record was matched to Raajit K. Rampal, and no figure has been checked by an editor.
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