Long-term hydroxyurea therapy alters bone marrow megakaryocyte morphology and associates with prognosis in myeloproliferative neoplasms.

Authors

Zhikang Zheng, Yingqing Xu, Tian Zeng, Rumeng Li, Bingbing Wen, Qingmei Han, Xiaojing Bao, Jian Huang

Published in

Annals of hematology. Volume 105. Issue 11. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

Hydroxyurea (HU) is a first-line treatment for myeloproliferative neoplasms (MPNs), but a quantitative, standardized framework for assessing its impact on megakaryocyte (MK) morphology and prognosis remains lacking. This retrospective, two-center study analyzed 22,097 MKs from 280 patients (118 polycythemia vera [PV], 162 essential thrombocythemia [ET]), classified into 12 subtypes using the 5th edition WHO classification in conjunction with objectively derived thresholds (minimum P-value approach). Our primary contribution is to establish a quantifiable scoring framework that translates descriptive WHO categories into reproducible prognostic metrics. Using this framework, HU significantly reduced normal MK proportion in JAK2-ET (P = 0.0189), TN-ET (P = 0.0233), and JAK2-PV (P = 0.0427), while increasing abnormal subtypes (bulbous, separated nuclear MKs); conversely, IFN was associated with preserved normal MKs and reduced abnormal forms. Multivariate Cox regression, applied to our empirically derived cutoffs, identified protective thresholds (normal MK ≥ 58% in ET, ≥ 53% in PV; emperipolesis ≥ 2% in ET) and adverse cutoffs (Naked nuclei ≥ 13% in ET, ≥ 7% in PV; staghorn like ≥ 6% in ET; separated nuclear ≥ 3% in ET) for myelofibrosis progression (all P < 0.05). Our quantitative findings corroborate prior qualitative observations that long-term HU is associated with adverse MK remodeling, while IFN correlates with lower progression risk as captured by our threshold-based system. This standardized scoring approach-not the identification of new prognostic factors-provides a reproducible tool for monitoring treatment-related morphological changes and may inform risk-adapted therapy in MPN patients.

PMID:
42902101
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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