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bioRxiv · 10.64898/2026.09.01.748468

Basophilic Erythroblast Emerges as the Key Turning Point in Polycythemia Vera

Konak, D.·Pir, P.
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Abstract

Abstract Polycythemia vera (PV) is a rare, chronic myeloproliferative neoplasm driven by the JAK2V617F mutation and characterized by uncontrolled erythroid proliferation. Although the mutation arises in hematopoietic stem cells, the differentiation stage at which its transcriptional consequences first become biologically meaningful has remained undefined. Using a multi-layer transcriptomics integration approach that combined differential gene expression, NicheNet ligand-receptor analysis, pseudotime trajectory inference, and CNV profiling on scRNA seq data, alongside bulk transcriptome validation, we identified basophilic erythroblasts as the critical transition point at which JAK2V617F shifts from a genomically present but transcriptionally silent state to an actively trajectory-altering and treatment-responsive disease driver. Differential expression revealed a qualitatively distinct disease signature at this stage, including ERFE-mediated iron dysregulation, MAP2K2-driven RAS/MAPK co-activation, and epigenetic reprogramming. NicheNet showed the establishment of a TGF{beta} superfamily and chemokine-driven niche-remodeling axis, and pseudotime analysis demonstrated that basophilic erythroblasts are the first erythroid population to exhibit condition-dependent trajectory divergence, whereas earlier progenitors showed none despite carrying the mutation. Interferon- treatment showed its broadest counterresponse at this stage but declined sharply thereafter, identifying basophilic erythroblasts as both the principal therapeutic target and the point of maximum vulnerability in PV.

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Konak, D., Pir, P.. 2026-09-01. Basophilic Erythroblast Emerges as the Key Turning Point in Polycythemia Vera. https://doi.org/10.64898/2026.09.01.748468

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