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Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
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Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies

Published on: November 10, 2023

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Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis

Nils B Leimkühler1, Hélène F E Gleitz1, Li Ronghui2

  • 1Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.

Cell Stem Cell
|December 10, 2020
PubMed

Insights

Researchers identified specific mesenchymal stromal cell (MSC) subsets driving myelofibrosis (MF) in myeloproliferative neoplasms (MPNs). Targeting the S100A8/S100A9 complex with tasquinimod showed therapeutic potential for MPNs and MF.

Area of Science:

  • Hematology
  • Oncology
  • Cell Biology

Background:

  • Myelofibrosis (MF) is a serious complication of myeloproliferative neoplasms (MPNs).
  • The precise roles of bone marrow microenvironment cells in MF pathogenesis are not fully understood.

Purpose of the Study:

  • To comprehensively map the bone marrow stroma in MPNs/MF at a single-cell level.
  • To identify specific cellular components contributing to MF development.

Main Methods:

  • Single-cell analysis of murine models and patient samples.
  • Functional characterization of mesenchymal stromal cell (MSC) subsets.
  • Assessment of S100A8/S100A9 expression in disease progression.
  • Evaluation of tasquinimod efficacy in JAK2V617F-mutated murine models.

Main Results:

  • Two distinct MSC subsets were identified as pro-fibrotic.
  • MSCs undergo stage-dependent functional reprogramming, losing progenitor status and gaining pro-fibrotic/inflammatory phenotypes.
  • S100A8/S100A9 expression in MSCs correlates with MF progression.
  • Tasquinimod treatment ameliorated MPN phenotype and fibrosis in murine models.

Conclusions:

  • Mesenchymal stromal cells play a critical role in MPN-associated myelofibrosis.
  • The S100A8/S100A9 complex is a key driver of MF progression and a potential therapeutic target.
  • Targeting S100A8/S100A9 signaling offers a promising therapeutic strategy for MPNs.
Keywords:
DAMPalarminsbiomarkerbone marrow fibrosisdrug targethematopoietic stem cellsmesenchymal stromal cellsmicroenvironmentmyeloproliferative neoplasmssingle cell RNA sequencing

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