JAK2

Overview

JAK2 encodes a non-receptor tyrosine kinase central to cytokine signaling; the V617F gain-of-function mutation defines myeloproliferative neoplasms and is also a high-risk clonal hematopoiesis driver.

Alterations observed in the corpus

  • JAK2 was identified as a high-risk clonal hematopoiesis (CH) genotype conferring particularly high risk of subsequent hematologic malignancy in 42,714 MSK patients with nonhematologic cancer profiled by MSK-IMPACT matched-normal sequencing PMID:38147626.
  • In 26 patients who developed a hematologic malignancy with paired post-diagnosis sequencing, JAK2 CH VAFs consistently expanded at disease onset (in contrast to DNMT3A and silent CH VAFs which mostly decreased) PMID:38147626.
  • Focal amplification identified in clear cell renal cell carcinoma (ccRCC) by TCGA comprehensive molecular characterization PMID:23792563
  • V617F present in 48/48 (100%) PV, 35/62 (56%) ET, and 27/39 (69%) MF patients; strictly mutually exclusive with CALR and MPL mutations in whole-exome sequencing of myeloproliferative neoplasms PMID:24325359
  • Co-amplified with CD274 (PD-L1) and PDCD1LG2 (PD-L2) at 9p24.1 in 15% of EBV-positive gastric adenocarcinoma (STAD) tumours (TCGA); elevated mRNA expression; supports rationale for JAK2 inhibitors and immune-checkpoint blockade in EBV-positive STAD PMID:25079317
  • Among 60 genes with COSMIC hotspot mutations identified as potential drug targets across non-clear cell RCC subtypes PMID:25401301
  • Identified as a marker of the immune-related ILC mRNA subtype in a comprehensive molecular analysis of invasive lobular carcinoma PMID:26451490
  • Recurrent driver in DLBCL (1001-patient cohort) but CRISPR knockout did NOT impair growth, suggesting JAK2 may act in early pathogenesis or via non-targetable functions in established DLBCL; cautions against naive mutation-based targeting. PMID:28985567
  • Mutations not associated with resistance to nivolumab in advanced melanoma (CA209-038, n=68), contrary to prior reports linking JAK pathway disruption to IFN-γ-blockade resistance. PMID:29033130
  • Homozygous loss-of-function JAK2 splice mutation with LOH identified in one NSCLC patient with primary resistance to anti-PD-(L)1 therapy (PD), consistent with interferon-gamma signaling defects; few total events in the 240-patient cohort PMID:29337640

Cancer types (linked)

  • Clonal hematopoiesis in patients with nonhematologic cancer — JAK2-mutant CH anticipates progression to hematologic malignancy PMID:38147626.

Co-occurrence and mutual exclusivity

  • Not specifically reported in the corpus.

Therapeutic relevance

  • JAK2-mutant CH may warrant closer hematologic surveillance in solid-tumor patients receiving genotoxic therapy PMID:38147626.

Open questions

  • The degree to which specific prior therapies drive expansion of JAK2 clones was not resolved PMID:38147626.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:23792563

This page was processed by crosslinker on 2026-05-14. - PMID:24325359

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

This page was processed by crosslinker on 2026-05-14. - PMID:25401301

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

This page was processed by crosslinker on 2026-05-14. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15. - PMID:29033130

This page was processed by entity-page-writer on 2026-05-15. - PMID:29337640

This page was processed by wiki-cli on 2026-05-15.