Genetic and Clinical Characteristics of Patients with Philadelphia-Negative Myeloproliferative Neoplasm Carrying Concurrent Mutations in JAK2V617F, CALR, and MPL

被引:3
作者
Wang, Yan [1 ]
Ran, Fei [2 ]
Lin, Jin [3 ]
Zhang, Jing [3 ]
Ma, Dan [1 ,4 ,5 ]
机构
[1] Guizhou Med Univ, Affiliated Hosp, Guizhou Prov Inst Hematol Malignancies, Dept Hematol, Guiyang, Peoples R China
[2] Guizhou Prov Peoples Hosp, Dept Clin Lab Med, Guiyang, Peoples R China
[3] Nanchang Univ, Affiliated Hosp 2, Dept Clin Lab, Jiangxi Prov Key Lab Lab Med, Nanchang, Peoples R China
[4] Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang, Peoples R China
[5] Guizhou Med Univ, Dept Hematol, Affiliated Hosp, 28 Guiyi St, Guiyang 550004, Guizhou, Peoples R China
基金
中国国家自然科学基金;
关键词
myeloproliferative neoplasms; CALR; MPL; gene mutation; coexistence; ESSENTIAL THROMBOCYTHEMIA; JAK2; V617F; CALRETICULIN MUTATIONS; SOMATIC MUTATIONS; POLYCYTHEMIA-VERA; CHINESE PATIENTS; COEXISTENCE; DELETION;
D O I
10.1177/15330338231154092
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simultaneous mutations in Janus kinase 2 (JAK2), calreticulin, and myeloproliferative leukemia (MPL) genes are generally not considered for characterizing Philadelphia-negative myeloproliferative neoplasms (MPNs), leading to misdiagnosis. Sanger sequencing and quantitative polymerase chain reaction were used to detect gene mutations in patients with MPN. We retrospectively screened the data of patients with double mutations in our center and from the PubMed database. Two patients tested positive for both JAK2V617F and CALR mutations (2/352 0.57%) in our center, while data of 35 patients from the PubMed database, including 26 patients with essential thrombocythemia (ET), 6 with primary myelofibrosis (PMF), 2 with unexplained thrombosis, and 1 with polycythemia vera were screened for double mutations. Among these mutations, co-mutation of JAKV617F-CALR constituted the majority (80.0%), when compared with JAKV617F-MPL (17.1%) and CALR-MPL (2.9%) mutations. Moreover, patients with concurrent mutational myeloproliferative neoplasm (MPN) were relatively older (P = .010) with significantly higher platelet counts than their counterparts with single gene mutations (P < .001). The occurrence of palpable splenomegaly (P < .001) and leukocyte count (P = .041) were also significantly different between patients with single and simultaneous gene mutations. These 4 risk factors also showed significant test effectiveness in the ET and PMF cohorts (P < .05). In terms of clinical characteristics of patients with ET, those with JAK2V617F-CALR mutation had higher but normal hemoglobin levels (P = .0151) than those carrying JAK2V617F-MPL mutation. From a clinical perspective, patients with multiple mutational MPN are different from those with single gene mutations. The poor treatment response by patients in our center and unfavorable indicators for patients with co-mutations in published literature indicate that customized treatment may be the best choice for patients with MPN carrying co-mutations.
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页数:10
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