Clinicopathologic Characteristics and Prognostic Profile of Chronic Myeloid Neoplasms With Somatic NF1 Mutations in Adult Patients.

Objectives: 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).

Methods: 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.

Results: 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).

Conclusions: 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.