Tariq Hamza, Loxas Margarita, Alikhan Mir B, Gao Juehua, Lu Xinyan, Chen Qing Ching, Chen Yi-Hua, Altman Jessica K, Jennings Lawrence J, Sukhanova Madina
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Pathology, Endeavor Health, Evanston, Illinois, USA.
Eur J Haematol. 2025 Jul;115(1):46-56. doi: 10.1111/ejh.14419. Epub 2025 Mar 28.
The clinicopathologic and prognostic features of somatic NF1 mutations have been well studied in pediatric myeloid neoplasms and adult acute myeloid leukemia (AML) but not in adult chronic myeloid neoplasms (CMNs), including myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs).
A retrospective review was performed to identify adult patients diagnosed with NF1-mutated CMNs between 1/2010 and 8/2023. Patients with NF1 wildtype (NF1-WT) CMNs concurrently diagnosed during the same time were used as a comparative group. Clinicopathologic and genetic characteristics and overall survival (OS) were compared between the two groups.
A total of 36 NF1-mutated CMNs were identified (4.7% of all CMNs), including 19 MDS, 4 MPNs, and 13 MDS/MPNs (all CMML). NF1-mutated CMMLs showed significantly higher absolute monocyte counts (AMC), more frequent complex karyotypes, and higher frequencies of SRSF2 and KRAS mutations compared to NF1-WT CMMLs. NF1-mutated MDS also showed significantly higher AMC, lower frequency of SF3B1, and higher frequencies of SRSF2 and KRAS mutations compared to NF1-WT MDS. The OS of NF1-mutated CMNs was significantly inferior to NF1-WT CMNs (median survival: 2.05 vs. 4.8 years; log-rank p = 0.03).
Adult CMNs with mutated NF1 show higher AMC, high-risk molecular cytogenetic features, and inferior survival. Therefore, testing for NF1 mutations could be considered part of risk assessment for patients with CMNs.
体细胞NF1突变的临床病理及预后特征在儿童髓系肿瘤和成人急性髓系白血病（AML）中已有充分研究，但在成人慢性髓系肿瘤（CMN）中尚未见报道，包括骨髓增生异常综合征（MDS）、骨髓增殖性肿瘤（MPN）和骨髓增生异常/骨髓增殖性肿瘤（MDS/MPN）。
进行回顾性研究，以确定2010年1月至2023年8月期间诊断为NF1突变型CMN的成年患者。将同期诊断的NF1野生型（NF1-WT）CMN患者作为对照组。比较两组的临床病理、遗传特征及总生存期（OS）。
共鉴定出36例NF1突变型CMN（占所有CMN的4.7%），包括19例MDS、4例MPN和13例MDS/MPN（均为慢性粒单核细胞白血病[CMML]）。与NF1-WT CMML相比，NF1突变型CMML的绝对单核细胞计数（AMC）显著更高，复杂核型更常见，SRSF2和KRAS突变频率更高。与NF1-WT MDS相比，NF1突变型MDS的AMC也显著更高，SF3B1频率更低，SRSF2和KRAS突变频率更高。NF1突变型CMN的OS显著低于NF1-WT CMN（中位生存期：2.05年对4.8年；对数秩检验p = 0.03）。
NF1突变的成人CMN表现出更高的AMC、高危分子细胞遗传学特征及较差的生存率。因此，NF1突变检测可被视为CMN患者风险评估的一部分。
