Park Chang-Hun, Kim Heyjin, Kim Boram, Yun Jae Won, Lee Ki-O, Yoo Keon Hee, Kim Hyun-Young, Kim Hee-Jin
Clin Lab. 2025 Jul 1;71(7). doi: 10.7754/Clin.Lab.2025.250321.
Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells that include BCR::ABL1-negative MPNs such as essential thrombocythemia (ET) and primary myelofibrosis (PMF). MPNs are rare in children, and knowledge of the genetics and biology of pediatric MPNs is very limited. Here, we report genetic variants in pediatric MPNs revealed by next generation sequencing (NGS).
The study included nine pediatric patients (eight with ET and one with PMF) consecutively diagnosed between January 2000 and June 2023. NGS was performed on an Ion S5 XL Sequencer with the OncomineTM myeloid research assay using bone marrow aspirate samples.
Five patients (56%) had clinically significant genetic variants. Two patients with ET had JAK2 V617F (driver) and two patients with ET had FLT3 E656A and ETV6 I10V, respectively. A single patient with PMF had 10 variants in eight genes, including two previously reported nonsense variants (ASXL1 W960* and TET2 R1452*) and three novel variants (BCOR A997E, TET2 I2002Mfs*12, and ZRSR2 F86_E102del). Of all, one patient (11%) experienced an event of transient ischemic attack with visual loss for 5 minutes and one patient with PMF expired of septic shock four months after diagnosis.
The results suggest a different genetic profile in pediatric MPN, with a lower incidence of driver variants in pediatric ET and multiple non-driver variants with poor prognostic implications in pediatric PMF.
骨髓增殖性肿瘤（MPN）是造血干细胞的克隆性疾病，包括BCR::ABL1阴性的MPN，如原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）。MPN在儿童中较为罕见，关于儿童MPN的遗传学和生物学知识非常有限。在此，我们报告通过下一代测序（NGS）揭示的儿童MPN中的基因变异。
该研究纳入了2000年1月至2023年6月期间连续诊断的9名儿科患者（8例ET和1例PMF）。使用骨髓穿刺样本，在Ion S5 XL测序仪上采用OncomineTM髓系研究分析方法进行NGS。
5名患者（56%）有具有临床意义的基因变异。2例ET患者有JAK2 V617F（驱动基因变异），另外2例ET患者分别有FLT3 E656A和ETV6 I10V。1例PMF患者在8个基因中有10个变异，包括2个先前报道的无义变异（ASXL1 W960和TET2 R1452）和3个新变异（BCOR A997E、TET2 I2002Mfs*12和ZRSR2 F86_E102del）。其中，1例患者（11%）经历了5分钟的短暂性脑缺血发作伴视力丧失，1例PMF患者在诊断后4个月死于感染性休克。
结果表明儿童MPN具有不同的基因特征，儿童ET中驱动基因变异的发生率较低，而儿童PMF中有多个具有不良预后意义的非驱动基因变异。
