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Peer-reviewedCC BY-NC-NDAnnals of hematology

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

  1. 1The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  2. 2The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
  3. 3The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].

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.

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BibTeX
@article{zheng2026longterm,
  title = {{Long-term hydroxyurea therapy alters bone marrow megakaryocyte morphology and associates with prognosis in myeloproliferative neoplasms.}},
  author = {Zhikang Zheng and Yingqing Xu and Tian Zeng and Rumeng Li and Bingbing Wen and Qingmei Han and Xiaojing Bao and Jian Huang},
  journal = {Annals of hematology},
  year = {2026},
  month = jul,
  doi = {10.1007/s00277-026-07202-x},
  url = {https://europepmc.org/article/MED/42902101},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Long-term hydroxyurea therapy alters bone marrow megakaryocyte morphology and associates with prognosis in myeloproliferative neoplasms.
AU  - Zhikang Zheng
AU  - Yingqing Xu
AU  - Tian Zeng
AU  - Rumeng Li
AU  - Bingbing Wen
AU  - Qingmei Han
AU  - Xiaojing Bao
AU  - Jian Huang
PY  - 2026
DA  - 2026/07/01
JO  - Annals of hematology
DO  - 10.1007/s00277-026-07202-x
UR  - https://europepmc.org/article/MED/42902101
AB  - 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.
SN  - 0939-5555
SN  - 1432-0584
ER  -