The prognostic impact of chromosome 7 with both arms loss [der(7)del(7p)del(7q)] in myelodysplastic syndrome/neoplasm

Chromosome 7 abnormality characterized by loss of both arms [der(7)del(7p)del(7q), hereafter ‘der(7)’] is very rare. The features and prognosis of patients with der(7) in myelodysplastic syndromes (MDS) remain unclear. We identified 35 MDS cases with der(7) using Metaphase Fluorescence In Situ Hybridization (metaphase-FISH), and compared them to 178 with del(7q), 390 with monosomy 7 (−7), and 603 with a normal karyotype (NK). Der(7) correlated with lower karyotypic complexity (odds ratios (ORs) 0.288, P = 0.001), more solitary abnormalities (ORs 3.652, P = 0.001), and frequent co-occurrence with −7 (40.9%; ORs 3.150, P = 0.004). Compared to NK, der(7) cases presented lower platelet counts, higher ferritin levels, and more frequent ≥3 mutations (P < 0.05). Mutations in ASXL1(ORs 2.394), RUNX1(ORs 2.618), SETBP1(ORs 15.132), and ETV6 (ORs 5.525) were enriched in der(7)/−7/del(7q) patients compared to NK (all P < 0.001), while NF1 (ORs 15.492, P = 0.002) and PTPN11 (ORs 6.653, P = 0.021) mutations were more prevalent in der(7) cases relative to NK. Prognostically, der(7) was identified as an independent risk factor (Hazard Ratios (HRs) 1.368, 95% CI 1.030–1.818; P = 0.031). Median overall survival (OS) of patients with der(7) was 17 months – shorter than NK (64 months, P = 0.005) but similar to −7 (20 months) and del(7q) (30 months). Hematopoietic stem cell transplantation improved survival (P = 0.018). Notably, 5 of 10 der(7) cases with follow-up evolved to −7. Der(7) defines a distinct high-risk subgroup with a unique molecular profile and poor prognosis comparable to −7.