JAK2 mutations to the fore in hereditary thrombocythemia

Langabeer, Stephen E.

doi:10.4161/21623988.2014.957618

Cited by 4 publications

(6 citation statements)

References 12 publications

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“…Computational tools predict a deleterious effect (ACMG criterion PP3). Pathogenic JAK2 variants can cause a type of hereditary thrombocythemia with autosomal dominant inheritance [ 25 ]. They mainly affect the two JAK homology domains in the C-terminal half of the protein.…”

Section: Resultsmentioning

confidence: 99%

NGS Evaluation of a Bernese Cohort of Unexplained Erythrocytosis Patients

Jalowiec

Vrotniakaite-Bajerciene

Capraru

et al. 2021

Genes

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(1) Background: Clinical and molecular data on patients with unexplained erythrocyto-sis is sparse. We aimed to analyze the clinical and molecular features of patients with congenital erythrocytosis in our tertiary reference center. (2) Methods: In 34 patients with unexplained erythrocytosis, a 13-gene Next-Generation Sequencing erythrocytosis panel developed at our center was conducted. (3) Results: In 6/34 (18%) patients, eight different heterozygous gene variants were found. These patients were, therefore, diagnosed with congenital erythrocytosis. Two patients had two different gene variants each. All variants were characterized as variants of unknown significance as they had not previously been described in the literature. The rest of the patients (28/34, 82%) had no detected gene variants. (4) Conclusions: Our experience shows that the NGS panel can be helpful in determining the reasons for persistent, unexplained erythrocytosis. In our cohort of patients with erythrocytosis, we identified some, thus far unknown, gene variants which may explain the clinical picture. However, further investigations are needed to determine the relationship between the molecular findings and the phenotype.

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Section: Resultsmentioning

confidence: 99%

NGS Evaluation of a Bernese Cohort of Unexplained Erythrocytosis Patients

Jalowiec

Vrotniakaite-Bajerciene

Capraru

et al. 2021

Genes

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“…JAK2 R938Q missense variant with 45% allele frequency was detected in a IR-exposed TN PMF patient (ID 1283) The JAK2 R938Q somatic mutation was reported previously in a hereditary thrombocythemia case and B-cell acute lymphoblastic leukemia case. 52,53 An IR-exposed PV patient (ID 1887) exhibited a frameshift variant JAK2 K539fs of uncertain biological significance with 23% allele frequency.…”

Section: Resultsmentioning

confidence: 99%

Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident

et al. 2018

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Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2, MPL and CALR genes, however, 10–15% of cases are triple negative (TN). A previous study showed lower rate of JAK2 V617F in Primary Myelofibrosis (PMF) patients exposed to low doses of ionizing radiation (IR) from Chernobyl accident. To examine distinct driver mutations, we enrolled 281 Ukrainian IR-exposed and unexposed MPN patients. Genomic DNA was obtained from peripheral blood leukocytes. JAK2 V617F, MPL W515, type 1- and 2-like CALR mutations were identified by Sanger Sequencing and RT-PCR. Chromosomal alterations were assessed by oligo-SNP microarray platform. Additional genetic variants were identified by whole exome and targeted sequencing. Statistical significance was evaluated by Fisher’s exact test and Wilcoxon’s rank sum test (R, version 3.4.2). IR-exposed MPN patients exhibited a different genetic profile versus unexposed: lower rate of JAK2 V617F (58.4% vs 75.4%, P = 0.0077), higher rate of type 1-like CALR mutation (12.2% vs 3.1%, P = 0.0056), higher rate of TN cases (27.8% vs 16.2%, P = 0.0366), higher rate of potentially pathogenic sequence variants (mean numbers: 4.8 vs 3.1, P = 0.0242). Furthermore, we identified several potential drivers specific to IR-exposed TN MPN patients: ATM p.S1691R with copy-neutral loss of heterozygosity at 11q; EZH2 p.D659G at 7q and SUZ12 p.V71M at 17q with copy number loss. Thus, IR-exposed MPN patients represent a group with distinct genomic characteristics worthy of further study.

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“…Hereditary thrombocytosis is a rare congenital hematologic disorder that is caused by single gene defects that affect only the megakaryocytic lineage, show polyclonal hematopoiesis and exhibit either an autosomal dominant or autosomal recessive Mendelian inheritance pattern. 1 , 2 A growing number of causative variants within the thrombopoietin ( THPO ) gene and the MPL proto-oncogene, thrombopoietin receptor ( MPL ) gene with different clinical characteristics have been described throughout the last decades and were reviewed by Teofili and Larocca. 2 More recently several variants within the JAK2 gene have been described in families with hereditary thrombocytosis which are germline and located in exons encoding either the kinase or pseudo-kinase domain of JAK2 .…”

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confidence: 99%

“…So far different single gene variants in the THPO , MPL , and JAK2 gene loci have been described as causes of hereditary thrombocytosis. 1 , 2 Depending on the location, the clinical relevance in respect to thrombocytosis-associated symptoms and the risk of thromboembolic events in particular differs widely among these variants. Several high risk variants as well as clinically silent variants have been described in the THPO , MPL , and JAK2 gene loci.…”

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confidence: 99%