Genetic and Clinical Characteristics of Patients with Philadelphia-Negative Myeloproliferative Neoplasm Carrying Concurrent Mutations in JAK2V617F, CALR, and MPL.
Genetic and Clinical Characteristics of Patients with Philadelphia-Negative Myeloproliferative Neoplasm Carrying Concurrent Mutations in JAK2V617F, CALR, and MPL.
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DOI：
10.1177/15330338231154092
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发表时间：
2023-01
影响因子：
2.8
通讯作者：
Ma, Dan
中科院分区：
文献类型：
--
作者：
Wang, Yan;Ran, Fei;Lin, Jin;Zhang, Jing;Ma, Dan
Janus激酶2（JAK 2），钙网蛋白和骨髓增生性白血病（MPL）基因的同时突变通常不被认为是费城阴性骨髓增生性肿瘤（MPN）的特征，导致误诊。采用桑格测序和定量聚合酶链反应检测MPN患者的基因突变。我们回顾性筛选了本中心和PubMed数据库中双突变患者的数据。我们中心的2例患者JAK 2 V617 F和CALR突变检测均为阳性（2/352 0.57%），而PubMed数据库中的35例患者的数据，包括26例原发性血小板增多症（ET），6例原发性骨髓纤维化（PMF），2例不明原因血栓形成，1例真性红细胞增多症，均进行了双突变筛查。在这些突变中，JAKV 617 F-CALR共突变占大多数（80.0%），而JAKV 617 F-MPL（17.1%）和CALR-MPL（2.9%）突变占大多数。此外，与单基因突变患者相比，同时发生突变骨髓增生性肿瘤（MPN）的患者年龄相对较大（P = 0.010），血小板计数显著较高（P <0.001）。单个和同时发生基因突变的患者之间可触及脾肿大（P <0.001）和白细胞计数（P = 0.041）的发生率也有显著差异。这4个危险因素在ET和PMF队列中也显示出显著的测试有效性（P <0.05）。在ET患者的临床特征方面，JAK 2 V617 F-CALR突变患者的血红蛋白水平高于JAK 2 V617 F-MPL突变患者，但正常（P = 0.0151）。从临床角度来看，多基因突变MPN患者与单基因突变患者不同。我们中心患者的治疗反应较差，并且已发表文献中存在共突变患者的不利指标表明，定制治疗可能是携带共突变的MPN患者的最佳选择。
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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