Cooccurring JAK2 V617F and R1063H mutations increase JAK2 signaling and neutrophilia in myeloproliferative neoplasms

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F18%3A73590410" target="_blank" >RIV/61989592:15110/18:73590410 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/18:00502682 RIV/00023736:_____/18:00012484

Result on the web

<a href="http://www.bloodjournal.org/content/bloodjournal/132/25/2695.full.pdf" target="_blank" >http://www.bloodjournal.org/content/bloodjournal/132/25/2695.full.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/blood-2018-04-843060" target="_blank" >10.1182/blood-2018-04-843060</a>

Result language

angličtina

Original language name

Cooccurring JAK2 V617F and R1063H mutations increase JAK2 signaling and neutrophilia in myeloproliferative neoplasms

Original language description

Clinical consequences of driver mutations in myeloproliferative neoplasms (MPNs) are well established, yet little is known about the impact of co-occurring JAK2 variants on the phenotype of MPNs. We tested a cohort of 390 JAK2 V617F-positive MPN patients for JAK2 R1063H, a variant previously described in polycythemia vera and hereditary erythrocytosis. We identified 14 carriers of both JAK2 V617F and JAK2 R1063H mutations. These patients exhibited significantly higher rate of neutrophilic granulocytosis compared to those harboring JAK2 V617F only. Quantification of R1063H allele in the genomic DNA samples indicated that the variant was inherited in 8 cases, with an allele burden around 50%. In 3 other patients with high JAK2 V617F allelic burden, the JAK2 R1063H was nearly homozygous (&gt;80%), suggesting the acquisition of the second allele by uniparental disomy. In 3 patients the R1063H mutation was acquired (allele percentage between 20.7% - 31.5%). Our functional studies demonstrated that the JAK2 V617F-induced signaling via the dimeric myeloid cytokine receptors is increased in the presence of the R1063H when the two mutations are in cis. Thus, acquisition of V617F in cis on a germline R1063H allele, or an acquisition of additional R1063H mutation increases JAK2 V617F oncogenic signaling that promotes neutrophilia.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30205 - Hematology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BLOOD

ISSN

0006-4971

e-ISSN

—

Volume of the periodical

132

Issue of the periodical within the volume

25

Country of publishing house

US - UNITED STATES

Number of pages

5

Pages from-to

2695-2699

UT code for WoS article

000453926500012

EID of the result in the Scopus database

2-s2.0-85058788204