Evaluation of the JAK2V617F mutational burden in patients with philadelphia chromosome negative myeloproliferative neoplasms: A single-center experience

Popova-Labachevska, Marija; Panovska-Stavridis, Irina; Eftimov, Aleksandar; Kapedanovska, Nestorovska A; Čevreska, Lidija; Ivanovski, Martin; Ridova, Nevenka; Trajkova, Sanja; Dimovski, Aleksandar

doi:10.2478/bjmg-2019-0021

Cited by 4 publications

(8 citation statements)

References 10 publications

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“…In our study, ET patients with high mutation loads of >50% showed lower hemoglobin levels, in line with some studies yet in contrast with most previous data [ 5 , 7 , 8 , 27 , 28 ]. In agreement with some previous studies but contrary to some others [ 4 , 5 , 7 , 8 , 27 , 28 ], we found no association with high mutation load or leukocyte count. We observed a trend towards lower platelet counts in ET patients with high mutation loads in line with the report published by Pich et al [ 27 ] yet contrary to most previous data.…”

Section: Discussionsupporting

confidence: 91%

“…Previous studies proposed different cut-off values for JAK2V617F allele load for the stratification of ET cases [ 2 , 4 , 5 , 7 , 8 , 24 , 25 , 26 , 27 , 28 ]. In our study, ET patients with high mutation loads of >50% showed lower hemoglobin levels, in line with some studies yet in contrast with most previous data [ 5 , 7 , 8 , 27 , 28 ]. In agreement with some previous studies but contrary to some others [ 4 , 5 , 7 , 8 , 27 , 28 ], we found no association with high mutation load or leukocyte count.…”

Section: Discussionmentioning

confidence: 99%

“…Most patients with PMF display intermediate-high levels of mutant allele burden while most PV patients have a higher mutant allele burden [ 2 ]. Studies investigating the correlation between JAK2V617F allele burden and clinical phenotype in Ph-negative MPNs have yielded inconsistent results [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. We investigated the impact of JAK2V617F allele burden on clinical and laboratory characteristics and outcomes in a total of 228 patients with Ph-negative MPNs (118 ET, 84 PMF, and 26 PV patients).…”

Section: Introductionmentioning

confidence: 99%

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Clinical Impact of JAK2V617F Allele Burden in Philadelphia-Negative Myeloproliferative Neoplasms

Yonal-Hindilerden

Şahin

Hindilerden

et al. 2023

Tjh

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Objective: The impact of JAK2V617F allele burden on clinical course in Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) is not clear. We analyzed the clinical impact of JAK2V617F allele burden in a relatively large series of patients with Ph-negative MPNs and long-term follow-up. Materials and Methods: A total of 228 patients with Ph-negative MPNs, including 118 with essential thrombocythemia (ET), 84 with primary myelofibrosis (PMF), and 26 with polycythemia vera (PV), were analyzed. The JAK2 MutaScreen assay was used to quantify JAK2V617F allele burden in genomic DNA. Results: In PV cases, high JAK2V617F allele burden was associated with a trend towards inferior overall survival. In ET, high JAK2V617F allele burden was associated with lower hemoglobin and hematocrit levels, higher lactate dehydrogenase (LDH) levels, larger spleen size, and increased bleeding and mortality rates. In PMF, high JAK2V617F allele burden was associated with higher leukocyte counts and larger spleen size. In the entire cohort, high allele burden was associated with higher leukocyte and lower platelet counts, higher LDH levels, larger spleen size, higher percentage of bleeding events, higher death rate, and inferior overall survival. Conclusion: Our results suggest that high JAK2V617F allele burdens are associated with more severe disease in PV and ET. In PMF, high JAK2V617F allele burdens were associated with more pronounced myeloproliferative phenotypes. In Ph-negative MPNs, high allele burdens were associated with more aggressive phenotypes. Our data with a long follow-up period support the possibility of JAK2V617F allele burden being used as a marker for predicting clinical phenotype in cases of Ph-negative MPNs.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical Impact of JAK2V617F Allele Burden in Philadelphia-Negative Myeloproliferative Neoplasms

Yonal-Hindilerden

Şahin

Hindilerden

et al. 2023

Tjh

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“…Variable level of JAK2 kinase activity as a reflection of the relative proportion of mutated and wild-type protein in the cell was one of them which gained much attention [19]. The concept of gene dosage postulates a counterpart between clinical manifestations and the proportion of JAK2V617F mutant alleles with the term 'allele burden' addressing the ratio of mutant and wild type JAK2 alleles in cells [24].…”

Section: Jak2v617f Allele Burdenmentioning

confidence: 99%

“…Multiple studies have shown a substantial differences of allele burden in different MPN phenotypes [19], [25]. In the majority of cases, the lowest allele burden was recorded in ET and higher allele burden in PV [24], [25], with PMF patients recording varied results [27]. An allele burden greater than 50% was observed to increase the probability of an overt PV or myelofibrotic evolution [28].…”

Section: Jak2 Allele Burden and Phenotypementioning

confidence: 99%

Review: JAK2V617F Allele Burden in Diagnosis and Therapeutic Monitoring of Myeloproliferative Neoplasms

Dharmawickreme

Witharana²

2023

EJMED

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Characterized by overproduction of differentiated cells of myeloid lineage, polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). Found in 95% of PV patients and 50-60% of ET and PMF patients, the JAK2V617F mutation is the most common molecular abnormality shared by the three MPN phenotypes. Although the JAK2 mutation is recommended for diagnosis of MPNs by the World Health Organization (WHO), its presence alone is insufficient to discriminate among the 3 subtypes. This implication of single mutation (JAK2V617F) in all three MPN phenotypes has long been an objective under question and several studies investigating on the gene dosage hypothesis have discovered the promising role of the JAK2V617F allele burden in MPN phenotype. The significant differences of the JAK2V617F allele burden in PV, ET and PMF patients as well its associations with specific clinical and haematological characteristics bear high utility in diagnosis, prognosis, and therapeutic monitoring. Although great strides have been achieved with the use of qPCR and new molecular biology techniques in allele burden quantification, addressing the deficits in the current understandings and further improvement of technology will be highly beneficial. Therefore, we have reviewed PubMed database from 2005 to 2022. Using keywords such as JAK2V617F mutation, Allele burden, Myeloproliferative neoplasms etc. and the present review discusses the significance of JAK2V617F allele burden in diagnosis and therapeutic monitoring of myeloproliferative neoplasms.

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Association of JAK2V617F allele burden and clinical correlates in polycythemia vera: a systematic review and meta-analysis

Chen,

Lin

et al. 2024

Ann Hematol

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Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.

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Evaluation of the JAK2V617F mutational burden in patients with philadelphia chromosome negative myeloproliferative neoplasms: A single-center experience

Cited by 4 publications

References 10 publications

Clinical Impact of JAK2V617F Allele Burden in Philadelphia-Negative Myeloproliferative Neoplasms

Clinical Impact of JAK2V617F Allele Burden in Philadelphia-Negative Myeloproliferative Neoplasms

Review: JAK2V617F Allele Burden in Diagnosis and Therapeutic Monitoring of Myeloproliferative Neoplasms

Association of JAK2V617F allele burden and clinical correlates in polycythemia vera: a systematic review and meta-analysis

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