WITHDRAWN: Molecular genetics of thrombotic myeloproliferative neoplasms: Implications in precision oncology

Chia, Yuh Cai; Ramli, Marini; Woon, Peng Yeong; Johan, Muhammad Farid; Hassan, Rosline; Islam, Asiful

doi:10.1016/j.gendis.2021.01.002

Cited by 5 publications

(3 citation statements)

References 213 publications

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“…The pathophysiology behind the thrombotic risk in PV is due to increased blood viscosity, secondary to high hematocrit levels, and the migration of platelets to the vessel wall and subsequent platelet activation [ 43 ]. As in ET, it may be due to increased myeloid production, activation of leukocytes, and endothelial dysfunction [ 44 ]. It is postulated that MPN clonal cells induce the release of inflammatory cytokines, which results in procoagulant states.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN)

Zulkeflee

Zulkafli

Johan

et al. 2021

IJERPH

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Mutations of JAK2V617F, CALR, and MPL genes confirm the diagnosis of myeloproliferative neoplasm (MPN). This study aims to determine the genetic profile of JAK2V617F, CALR exon 9 Type 1 (52 bp deletion) and Type 2 (5 bp insertion), and MPL W515 L/K genes among Malaysian patients and correlate these mutations with clinical and hematologic parameters in MPN. Mutations of JAK2V617F, CALR, and MPL were analyzed in 159 Malaysian patients using allele-specific polymerase chain reaction, including 76 polycythemia vera (PV), 41 essential thrombocythemia (ET), and 42 primary myelofibrosis (PMF) mutations, and the demographics of the patients were retrieved. The result showed that 73.6% JAK2V617F, 5.66% CALR, and 27.7% were triple-negative mutations. No MPL W515L/K mutation was detected. In ET and PMF, the predominance type was the CALR Type 1 mutation. In JAK2V617F mutant patients, serum LDH was significantly higher in PMF compared to PV and ET. PV has a higher risk of evolving to post PV myelofibrosis compared to ET. A thrombotic event at initial diagnosis of 40.9% was high compared to global incidence. Only one PMF patient had a CALR mutation that transformed to acute myeloid leukemia. JAK2V617F and CALR mutations play an important role in diagnostics. Hence, every patient suspected of having a myeloproliferative neoplasm should be screened for these mutations.

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Section: Discussionmentioning

confidence: 99%

Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN)

Zulkeflee

Zulkafli

Johan

et al. 2021

IJERPH

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“…Several common thrombophilia markers are associated with an increased risk of developing vascular events in patients with PV (reviewed in [ 155 ]), including high levels of C-reactive protein in blood serum and SNVs in the factor V-Leiden ( F5 ) gene [ 156 , 157 , 158 ]. Higher factor VIII levels, a known risk factor for venous thrombosis and coronary artery disease [ 159 ], were identified in PV patients compared to healthy subjects, with levels of 141 versus 98 IU/dL, respectively [ 160 ].…”

Section: Prognosismentioning

confidence: 99%

Recent Advances in the Use of Molecular Analyses to Inform the Diagnosis and Prognosis of Patients with Polycythaemia Vera

Stuckey

Gómez‐Casares

2021

IJMS

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Genetic studies in the past decade have improved our understanding of the molecular basis of the BCR-ABL1-negative myeloproliferative neoplasm (MPN) polycythaemia vera (PV). Such breakthroughs include the discovery of the JAK2V617F driver mutation in approximately 95% of patients with PV, as well as some very rare cases of familial hereditary MPN caused by inherited germline mutations. Patients with PV often progress to fibrosis or acute myeloid leukaemia, both associated with very poor clinical outcome. Moreover, thrombosis and major bleeding are the principal causes of morbidity and mortality. As a result of increasingly available and economical next-generation sequencing technologies, mutational studies have revealed the prognostic relevance of a few somatic mutations in terms of thrombotic risk and risk of transformation, helping to improve the risk stratification of patients with PV. Finally, knowledge of the molecular basis of PV has helped identify targets for directed therapy. The constitutive activation of the tyrosine kinase JAK2 is targeted by ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor for PV patients who are resistant or intolerant to cytoreductive treatment with hydroxyurea. Other molecular mechanisms have also been revealed, and numerous agents are in various stages of development. Here, we will provide an update of the recent published literature on how molecular testing can improve the diagnosis and prognosis of patients with PV and present recent advances that may have prognostic value in the near future.

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“…Three main driver gene mutations, Janus kinase 2 ( JAK2 ), Thrombopoietin receptor ( MPL ) and Calreticulin ( CALR ), have been identified in association with MPN and may have an important role in assisting the diagnosis of MPN [ 4 ]. In addition, epigenetic modification genes such as TET2 , ASXL1 , DNMT3A and EZH2 are also commonly mutated in cases of MPN with a frequency of 1–30% [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Prevalence of TET2 Gene Mutations in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms (MPN): A Systematic Review and Meta-Analysis

Chia

Islam

Hider

et al. 2021

Cancers

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Multiple recurrent somatic mutations have recently been identified in association with myeloproliferative neoplasms (MPN). This meta-analysis aims to assess the pooled prevalence of TET2 gene mutations among patients with MPN. Six databases (PubMed, Scopus, ScienceDirect, Google Scholar, Web of Science and Embase) were searched for relevant studies from inception till September 2020, without language restrictions. The eligibility criteria included BCR-ABL-negative MPN adults with TET2 gene mutations. A random-effects model was used to estimate the pooled prevalence with 95% confidence intervals (CIs). Subgroup analyses explored results among different continents and countries, WHO diagnostic criteria, screening methods and types of MF. Quality assessment was undertaken using the Joanna Briggs Institute critical appraisal tool. The study was registered with PROSPERO (CRD42020212223). Thirty-five studies were included (n = 5121, 47.1% female). Overall, the pooled prevalence of TET2 gene mutations in MPN patients was 15.5% (95% CI: 12.1–19.0%, I2 = 94%). Regional differences explained a substantial amount of heterogeneity. The prevalence of TET2 gene mutations among the three subtypes PV, ET and MF were 16.8%, 9.8% and 15.7%, respectively. The quality of the included studies was determined to be moderate–high among 83% of the included studies. Among patients with BCR-ABL-negative MPN, the overall prevalence of TET2 gene mutations was 15.5%.

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WITHDRAWN: Molecular genetics of thrombotic myeloproliferative neoplasms: Implications in precision oncology

Cited by 5 publications

References 213 publications

Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN)

Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN)

Recent Advances in the Use of Molecular Analyses to Inform the Diagnosis and Prognosis of Patients with Polycythaemia Vera

The Prevalence of TET2 Gene Mutations in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms (MPN): A Systematic Review and Meta-Analysis

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