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December 8, 2025BloodOpen Access

Tissue specific requirement for the inv(16) oncogene CBFB::MYH11 implies unique leukemia survival mechanisms in the bone marrow microenvironment

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Authors

SPSipra PandaMBMichelle BeckerCRCecilia Rivas

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Overview

Inhibitors targeting oncogene CM in leukemia show diverse survival mechanisms in the bone marrow, implying treatment strategies may need adaptation.

Key Points

  • To investigate the role of the CBFB::MYH11 oncogene in leukemia survival mechanisms within the bone marrow microenvironment.
  • Used a knockin mouse model expressing the fusion gene under the Mx-1 promoter.
  • Transduced leukemia cells with doxycycline-inducible shRNA targeting MYH11.
  • Performed transplantation of modified leukemia cells into irradiated mice and monitored engraftment.
  • Conducted bulk and single-cell RNA sequencing to analyze gene expression changes.
  • Decreased CM expression nearly eliminated leukemia cells in the peripheral blood and spleen by day 7 of treatment.
  • Evidence of unique survival mechanisms in the bone marrow, with over 20% leukemia cells persisting despite reduced CM levels.
  • Autophagy-associated genes showed significant upregulation in CM knockdown bone marrow cells, indicating a survival pathway.

Cite This Study

Panda et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d578https://doi.org/10.1182/blood-2025-3225
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