Genetic Characteristics of Patients with Young-Onset Myelodysplastic Neoplasms.

Myelodysplastic neoplasm (MDS) is a heterogeneous group of myeloid neoplasms affected by germline and somatic genetic alterations. The incidence of MDS increases with age but rarely occurs at a young age. We investigated the germline and somatic genetic alterations of Korean patients with young-onset MDS (<40 years). Among the thirty-one patients, five (16.1%) had causative germline variants predisposing them to myeloid neoplasms (three with variants and one each with and variants). We found that PGM3 deficiency, a subtype of severe immunodeficiency, predisposes patients to MDS. Somatic mutations were identified in 14 patients (45.2%), with lower rates in patients aged < 20 years (11.1%). Nine (29%) patients had S34F/Y mutations, and patients with mutations showed significantly worse progression-free survival ( < 0.001) and overall survival ( = 0.006) than those without mutations. A M41T mutation that causes VEXAS syndrome was identified in a male patient. In conclusion, a germline predisposition to myeloid neoplasms occurred in ~16% of young-onset MDS patients and was largely associated with primary immunodeficiencies, including GATA2 deficiency. Furthermore, the high frequency of somatic mutations in patients with young-onset MDS suggests the presence of a distinct MDS subtype.