Triple Gene Detection of CALR, JAK2(V617F) or MPL(W515L/K) Mutation to Predict Thrombosis and Splenomegaly Risk in Essential Thrombocythemia and Primary Myelofibrosis Patients: A Systematic Review and Meta-Analysis

Abstract

Objective: To determine the association between CALR, JAK2 (V617F) and MPL (W515L/K) mutations and the risk of thrombosis and splenomegaly in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. Method: Medline and Web of Science were searched with the restrictions between January 2014 to October 2019.Two researchers independently extracted study data and outcomes. The main outcome measures were patients’ gene mutation detection results and corresponding states of thrombosis(artery or venous) and splenomegaly. Odds ratios (OR) were calculated by random effects models. Results:After the 2890 studies identified, 15 studies were opted for data analysis. All the study data were from clinical sources, publication bias were assessed to be eligible. In spite of the different regional sources, no obvious heterogeneity was found in this analysis (I2 0·10). In CALR mutation patients, 129 out of 862(15·0%) vs 93 out of 723(12·9%) triple-negtive control had thrombosis, and 145 out of 435(33·3%) vs 119 out of 435(27·4%) triple-negtive control had splenomegaly. For JAK2(V617F) positive patients, 623 out of 2496 (25·0%) vs 100 out of 748(13.3%) triple-negtive control had thrombosis, and 371 out of 1148(32·3%) vs 77 out of 354(21·8%) triple-negtive control had splenomegaly. And for MPL(W515L/K) positive patients, 36 out of 125(28·8%) vs 78 out 581(13·4%) triple-negtive control had thrombosis, and 15 out of 48(31·3%) vs 41 out of 254(16·1%) triple-negtive control had splenomegaly. Conclusion: The JAK2(V617F) and MPL(W515L/K) mutations were associated with higher risks of thrombosis, and all the CALR, JAK2(V617F) and MPL(W515L/K) mutations were associated with a middle risk of splenomegaly. Funding Statement: This research work was supported by National Natural Science Foundation of China (Grant No. 81973180 and No. 81673298), Natural Science Foundation of the Jiangsu Higher Education Institutions of China for Excellent Young Talents (Grant No. BK20180077), the Drug Innovation Major Project (2019ZX09301142). Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: that they have no relationships with companies that might have an interest in the submitted work in the previous 3 years; their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and they have no non-financial interests that may be relevant to the submitted work.