Deciphering the complex clonal heterogeneity of polycythemia vera and the response to interferon alfa.

ABSTRACT:

Abstract

Interferon alfa (IFN-α) is approved for the therapy of patients with polycythemia vera (PV), a subtype of myeloproliferative neoplasm (MPN). Some patients achieve molecular responses (MRs), but clonal factors sensitizing for MRs remain elusive. We integrated colony formation assays with single-cell RNA sequencing (scRNA-seq) and genotyping in PV-derived cells and healthy controls (HCs) to dissect how IFN-α targets diseased clones during erythroid differentiation. IFN-α significantly decreased colony growth in MPNs and HCs with variable transcriptional responses observed in individual colonies. scRNA-seq of colonies demonstrated more mature erythroid colonies in PV than HCs. JAK2V617F-mutant cells exhibited upregulated STAT5A, heme, and G2M checkpoint pathways compared with

SUBMITTER: Kalmer M 

PROVIDER: S-EPMC12008703 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature