Differential Expression of PRDM16 and PRDM14 in Myeloproliferative Neoplasms as Compared to Normal Bone Marrow: A Pilot Study

PRDM family transcription factors have been implicated in hematopoietic regulation, yet their expression in classical Philadelphia-negative myeloproliferative neoplasms (MPNs) remains unexplored. We investigated PRDM14 and PRDM16 expression in bone marrow samples from MPN patients and controls to assess associations with proliferative activity. Bone marrow trephine biopsies were obtained from 11 cases (5 with normal histology; 6 with pathological histology). Clinical, morphological, and molecular data (JAK2 mutation status) were collected. Paraffin-embedded sections were analyzed via immunofluorescence using monoclonal antibodies against PRDM14, PRDM16, and Ki67. Imaging was performed on a Zeiss Axio Imager.Z2 and quantified with ImageJ. Statistical analyses included Welch’s t-test, cluster-robust OLS regres-sion, and correlation analyses, with patient-level clustering considered in all analyses. PRDM16⁺ cell density and PRDM16⁺Ki67⁺ double-positive subsets showed a consistent trend toward higher values in patients compared with controls, approaching statistical significance when accounting for patient-level clustering (mean ± 95% CI 499.8 [360.4–639.2] vs. 309.4 [176.4–442.5] cells/mm² , p=0.060 and 96.5 [68.3-124.7] vs. 191.3 [89.3-293.3] cells/mm², p=0.08, respectively). In contrast, PRDM14⁺ and PRDM14⁺Ki67⁺ populations were similarly low in both groups. Inter-patient variability among MPN cases was not significantly altered. Both PRDM16 and PRDM14 expression correlated positively with proliferative activity measured by Ki67 expression, with robust associ-ations even in small subgroups (PRDM16⁺Ki67⁺ vs. Ki67⁺: r=0.809, p=0.003 and PRDM14⁺Ki67⁺ vs. Ki67⁺: r=0.744, p=0.009 for n=11). PRDM16 and PRDM14 expression themselves were not directly correlated (r = 0.518, p > 0.1). Our data provide the first evidence of differential PRDM14 and PRDM16 expression in human MPNs. These findings highlight mechanistically PRDM16 as a potential marker of malignant prolif-eration in MPNs and establish a foundation for further studies.