DARS expression in JAK2V617F-positive myeloproliferative neoplasms: immunohistochemical analysis and clinical associations

Abstract

Aspartyl-tRNA synthetase (DARS) is implicated in several cancers, but its role in BCR::ABL-negative JAK2V617F-positive myeloproliferative neoplasms (MPNs) is unclear. This study evaluated DARS expression in MPN subtypes and its associations with clinical parameters and survival. Diagnostic bone marrow biopsies from 121 JAK2V617F-positive MPN patients (PV, n = 34; ET, n = 25; PMF, n = 54; MPN-U, n = 8) were stained on a Ventana BenchMark XT immunostainer using anti-DARS antibody (ABclonal A6574). DARS immunoreactive score (IRS) was determined by multiplying intensity (0–3) and percentage of positive cells (0–4). Inter-observer agreement was excellent (κ = 0.89, 95% CI: 0.83–0.95). Patients were stratified using the cohort’s median cutoff (IRS = 9) for survival analysis. Statistical tests included Kruskal-Wallis with effect sizes and multivariate Cox regression. DARS IRS differed across subtypes (H = 14.19, p = 0.003, η²=0.10): PV median 9 with IQR (9–12), ET 9 (8–12), PMF 8 (6–9), and MPN-U 10.5 (6–12). PV vs. PMF differences: intensity p = 0.001 (r = 0.35), IRS p < 0.001 (r = 0.38). DARS IRS correlated inversely with spleen size (ρ=–0.266, p = 0.003, 95% CI: − 0.43 to − 0.09), LDH (ρ=–0.194, p = 0.033), and fibrosis grade (ρ=–0.280, p = 0.002), and positively with hemoglobin (ρ = 0.308, p = 0.001, 95% CI: 0.13–0.47). High DARS expression independently predicted improved leukemia-free survival (LFS) (HR = 0.42, p = 0.007, 95% CI: 0.22–0.80) after adjusting for age, subtype, and fibrosis. DARS is differentially expressed in MPN subtypes. Its association with enhanced LFS identifies DARS as a potential prognostic biomarker warranting validation in larger cohorts.