Clinical and histopathological features of myeloid neoplasms with concurrent Janus kinase 2 (JAK2) V617F and KIT proto-oncogene, receptor tyrosine kinase (KIT) D816V mutations

• Verfasst von: Naumann, Nicole [VerfasserIn]
• Verfasst von: Lübke, Johannes [VerfasserIn]
• Verfasst von: Shomali, William [VerfasserIn]
• Verfasst von: Reiter, Lukas [VerfasserIn]
• Verfasst von: Horny, Hans-Peter [VerfasserIn]
• Verfasst von: Jawhar, Mohamad [VerfasserIn]
• Verfasst von: Dangelo, Vito [VerfasserIn]
• Verfasst von: Fabarius, Alice [VerfasserIn]
• Verfasst von: Metzgeroth, Georgia [VerfasserIn]
• Verfasst von: Kreil, Sebastian [VerfasserIn]
• Verfasst von: Sotlar, Karl [VerfasserIn]
• Verfasst von: Oni, Claire [VerfasserIn]
• Verfasst von: Harrison, Claire [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Verfasst von: Cross, Nicholas C. P. [VerfasserIn]
• Verfasst von: Valent, Peter [VerfasserIn]
• Verfasst von: Radia, Deepti [VerfasserIn]
• Verfasst von: Gotlib, Jason [VerfasserIn]
• Verfasst von: Reiter, Andreas [VerfasserIn]
• Verfasst von: Schwaab, Juliana [VerfasserIn]
• Titel: Clinical and histopathological features of myeloid neoplasms with concurrent Janus kinase 2 (JAK2) V617F and KIT proto-oncogene, receptor tyrosine kinase (KIT) D816V mutations
• Verf.angabe: Nicole Naumann, Johannes Lübke, William Shomali, Lukas Reiter, Hans-Peter Horny, Mohamad Jawhar, Vito Dangelo, Alice Fabarius, Georgia Metzgeroth, Sebastian Kreil, Karl Sotlar, Claire Oni, Claire Harrison, Wolf-Karsten Hofmann, Nicholas C. P. Cross, Peter Valent, Deepti Radia, Jason Gotlib, Andreas Reiter and Juliana Schwaab
• E-Jahr: 2021
• Jahr: 1 June 2021
• Umfang: 11 S.
• Fussnoten: Gesehen am 27.10.2023
• Titel Quelle: Enthalten in: British journal of haematology
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1955
• Jahr Quelle: 2021
• Band/Heft Quelle: 194(2021), 2, Seite 344-354
• ISSN Quelle: 1365-2141
• DOI: doi:10.1111/bjh.17567
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: JAK2 V617F
• Sach-SW: KIT D816V
• Sach-SW: mixed phenotype
• Sach-SW: multi-mutated myeloid neoplasm
• Sach-SW: myeloproliferative neoplasm
• Sach-SW: systemic mastocytosis
• K10plus-PPN: 1868576116
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

We report on 45 patients with myeloid neoplasms and concurrent Janus kinase 2 (JAK2) V617F and KIT proto-oncogene, receptor tyrosine kinase (KIT) D816V (JAK2pos./KITpos.) mutations, which are individually identified in >60% of patients with classical myeloproliferative neoplasms (MPN) and >90% of patients with systemic mastocytosis (SM) respectively. In SM, the concurrent presence of a clonal non-mast cell neoplasm [SM with associated haematological neoplasm (SM-AHN)] usually constitutes a distinct subtype associated with poor survival. All 45 patients presented with a heterogeneous combination of clinical/morphological features typical of the individual disorders (e.g. leuco-/erythro-/thrombocytosis and elevated lactate dehydrogenase for MPN; elevated serum tryptase and alkaline phosphatase for SM). Overlapping features identified in 70% of patients included splenomegaly, cytopenia(s), bone marrow fibrosis and additional somatic mutations. Molecular dissection revealed discordant development of variant allele frequency for both mutations and absence of concurrently positive single-cell derived colonies, indicating disease evolution in two independent clones rather than monoclonal disease in >60% of patients examined. Overall survival of JAK2pos./KITpos. patients without additional somatic high-risk mutations [HRM, e.g. in serine and arginine-rich splicing factor 2 (SRSF2), additional sex combs like-1 (ASXL1) or Runt-related transcription factor 1 (RUNX1)] at 5 years was 77%, indicating that the mutual impact of JAK2 V617F and KIT D816V on prognosis is fundamentally different from the adverse impact of additional HRM in the individual disorders.