Clinical characteristics and whole exome sequencing in JAK2V617F- and CALR-unmutated essential thrombocythemia.

IF 2 4区医学 Q3 HEMATOLOGY

Hematology Pub Date : 2026-12-01 Epub Date: 2026-01-21 DOI:10.1080/16078454.2026.2616933

Siraphop Thammayot, Patcharawadee Thongkumkoon, Jeerawan Klangjorhor, Noppamas Panyasit, Piangrawee Niprapan, Nonthakorn Hantrakun, Teerachat Punnachet, Pokpong Piriyakhuntorn, Thanawat Rattanathammethee, Sasinee Hantrakool, Adisak Tantiworawit, Lalita Norasetthada, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong

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引用次数: 0

Abstract

Objectives: The aim of this study was to characterize the clinical features and outcomes of patients with JAK2 V617F- and CALR-unmutated essential thrombocythemia (ET) and to identify potential driver mutations through whole-exome sequencing (WES).

Methods: This was a cross-sectional study including patients diagnosed with ET between 2007 and 2024. Clinical characteristics and outcomes were compared between patients with and without JAK2V617F and CALR mutations. WES was analyzed in JAK2V617F- and CALR-unmutated ET patients.

Results: Thirty-nine out of 162 ET patients (24%) were JAK2V617F- and CALR-unmutated. This group was younger than patients in the JAK2V617F mutated group (mean age 53.7 vs. 61.1 years, p = 0.012) and had lower incidence of thrombotic events (5.1% vs. 9.1%, p = 0.327). The median overall survival was 13.51 years compared to 12.61 years in patients with JAK2V617F or CALR mutations (p = 0.63). There were no statistically significant differences in clinical symptoms, incidence of thrombosis, bleeding, myelofibrosis, or leukemic transformation. WES was analyzed in 15 patients. Uncommon MPL mutations were identified, including MPLL265F, MPLP70L, and MPLR321Q. Potential novel CALR mutations were detected in exon 5 (c.540C > T, N180 = ) and exon 6 (c.703-3del). Non-driver gene mutations were detected, including RUNX1 (57.1%), ASXL1, DNMT3A, SETBP1, and MSH6.

Discussion and conclusions: Patients with JAK2V617F- and CALR-unmutated ET tend to present at a younger age and exhibit a lower incidence of thrombosis compared to those with JAK2V617F-mutated ET. The application of WES enabled the detection of uncommon and potential driver mutations in JAK2V617F- and CALR-unmutated ET.

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JAK2V617F和calr未突变的原发性血小板增多症的临床特征和全外显子组测序

目的：本研究的目的是表征JAK2 V617F和calr未突变的原发性血小板增生症（ET）患者的临床特征和结果，并通过全外显子组测序（WES）识别潜在的驱动突变。方法：这是一项横断面研究，包括2007年至2024年间诊断为ET的患者。比较JAK2V617F和CALR突变患者和非JAK2V617F突变患者的临床特征和结果。在JAK2V617F和calr未突变的ET患者中分析WES。结果：162例ET患者中有39例（24%）JAK2V617F和calr未突变。该组患者比JAK2V617F突变组患者年轻（平均年龄53.7岁vs. 61.1岁，p = 0.012），血栓事件发生率较低（5.1% vs. 9.1%, p = 0.327）。JAK2V617F或CALR突变患者的中位总生存期为13.51年，而JAK2V617F或CALR突变患者为12.61年（p = 0.63）。两组在临床症状、血栓、出血、骨髓纤维化或白血病转化发生率方面无统计学差异。对15例患者进行WES分析。发现了不常见的MPL突变，包括MPLL265F、MPLP70L和MPLR321Q。在外显子5 （c.540C > T, N180 =）和外显子6 （c.703-3del）检测到潜在的新CALR突变。检测到非驱动基因突变，包括RUNX1（57.1%）、ASXL1、DNMT3A、SETBP1和MSH6。讨论和结论：与JAK2V617F和calr未突变的ET相比，JAK2V617F和calr未突变的ET患者往往更年轻，血栓发生率更低。WES的应用能够检测到JAK2V617F和calr未突变的ET中不常见和潜在的驱动突变。

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来源期刊

Hematology 医学-血液学

CiteScore

2.60

自引率

5.30%

发文量

140

审稿时长

3 months

期刊介绍： Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.