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December 8, 2025BloodOpen Access

Thrombopoietin inhibition abrogates JAK2V617F clonal expansion in a murine model of myeloproliferative neoplasm

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Authors

CLChristina U. Lorentz

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Overview

Experimental findings reveal that targeting TPO effectively reduces JAK2V617F clonal expansion in MPN models, indicating a potential therapeutic approach alongside JAK2 inhibition.

Key Points

  • To evaluate the therapeutic potential of TPO inhibition in reducing JAK2V617F clonal expansion in murine MPN models.
  • Utilized transgenic JAK2V617F mouse models and competitive transplantation.
  • Investigated the effects of Thpo antisense oligonucleotide and ruxolitinib on MPN phenotypes.
  • Measured blood cell counts, plasma TPO levels, and megakaryocyte density in treatment groups.
  • ASO reduced Thpo expression by 83% and plasma TPO by 100% in treated mice.
  • Platelet counts were significantly reduced after ASO treatment compared to saline.
  • JAK2V617F clonal expansion was more effectively suppressed with ASO than with ruxolitinib alone.

Cite This Study

Christina U. Lorentz (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd65https://doi.org/10.1182/blood-2025-1987
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Selective ASO-based JAK2 inhibitor for the treatment of hematological malignancies with JAK2 V617F mutation burden2025
  2. 2Hepatic thrombopoietin gene silencing reduces platelet count and breast cancer progression in transgenic MMTV-PyMT mice2019 · 56 citations
  3. 3Single-cell transcriptomic studies reveal altered heterogeneity in CD41 enriched megakaryocytes after targeted therapy in myeloproliferative neoplasm2025
  4. 4Direct small molecule inhibition of RAS enhances JAK2 inhibitor therapy in preclinical models of myeloproliferative neoplasms2025
  5. 5Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease2024 · 3 citations