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December 8, 2025Blood

Momelotinib-mediated transcriptional reprogramming induces synthetic lethal interaction with calcineurin-NFAT signaling

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Authors

MKMeenu KesarwaniZKZachary KincaidJSJoshua Schwieterman

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Overview

Analysis reveals momelotinib and calcineurin inhibitors achieve curative responses in acute myeloid leukemia, suggesting novel therapeutic strategies to overcome resistance.

Key Points

  • Momelotinib treatment achieved a curative response in a high-risk murine AML model treated with calcineurin inhibitors.
  • Gilteritinib depletion of genes involved in DNA synthesis and the role of P53 loss in resistance were confirmed.
  • Chemical-genetic screen utilizing CRISPR-Cas9 identified unique drug-induced dependencies, enhancing targeted treatments.
  • Combination therapy highlights a robust therapeutic window, selectively targeting leukemic cells while preserving normal hematopoiesis.

Cite This Study

Kesarwani et al. (2025) studied this question.

synapsesocial.com/papers/69362f714fa91c937236e199https://doi.org/10.1182/blood-2025-756
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