Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia.
Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia.
Int J Environ Res Public Health. 2021 Jul 16;18(14):7582. doi: 10.3390/ijerph18147582.
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.
JAK2V617F、CALR 和 MPL 基因突变可明确骨髓增殖性肿瘤(MPN)的诊断。本研究旨在确定马来西亚患者 JAK2V617F、CALR 外显子 9 型 1(52bp 缺失)和 2(5bp 插入)以及 MPL W515L/K 基因的遗传特征,并将这些突变与 MPN 中的临床和血液学参数相关联。采用等位基因特异性聚合酶链反应对 159 例马来西亚患者的 JAK2V617F、CALR 和 MPL 突变进行分析,包括 76 例真性红细胞增多症(PV)、41 例原发性血小板增多症(ET)和 42 例原发性骨髓纤维化(PMF)突变,并检索患者的人口统计学资料。结果显示,73.6%为 JAK2V617F 突变、5.66%为 CALR 突变、27.7%为三阴性突变。未检测到 MPL W515L/K 突变。在 ET 和 PMF 中,优势类型为 CALR 型 1 突变。在 JAK2V617F 突变患者中,与 PV 和 ET 相比,PMF 患者血清 LDH 显著升高。与 ET 相比,PV 发展为 PV 后骨髓纤维化的风险更高。与全球发病率相比,初诊时发生血栓事件的比例较高,为 40.9%。只有 1 例 PMF 患者的 CALR 突变转化为急性髓系白血病。JAK2V617F 和 CALR 突变在诊断中起重要作用。因此,每个疑似患有骨髓增殖性肿瘤的患者都应进行这些突变的筛查。