2. Academic Validation
  3. Schlafen 12 modulation and targeting in acute myeloid leukemia

Schlafen 12 modulation and targeting in acute myeloid leukemia

  • Cancer Res Commun. 2025 Oct 29. doi: 10.1158/2767-9764.CRC-25-0283.
Jamie N Guillen Magaña 1,  Markella Zannikou 2,  Aneta Baran 3,  Sara Small 4,  Michael Schieber 5,  Matthew J Schipma 6,  Elizabeth T Bartom 7,  Masha Kocherginsky 8,  Diana Saleiro 9,  Elspeth M Beauchamp 10,  Frank Eckerdt 11,  Leonidas C Platanias 9
Affiliations

Affiliations

  • 1 Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United States.
  • 2 Northwestern University, United States.
  • 3 Northwestern University, Chicago, Illinois, United States.
  • 4 Fox Chase Cancer Center, United States.
  • 5 Northwestern University, Chicago, United States.
  • 6 Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
  • 7 NORTHWESTERN UNIVERSITY AT CHICAGO, Chicago, IL, United States.
  • 8 Northwestern University Feinberg School of Medicine, Chicago, Il, United States.
  • 9 Northwestern University, Chicago, IL, United States.
  • 10 Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
  • 11 Northwestern University, Feinberg School of Medicine, Chicago, Illinios, United States.
PMID: 41150877 DOI: 10.1158/2767-9764.CRC-25-0283
Abstract

We examined the role of SLFN12, a member of the Schlafen (SLFN) family of interferon-regulated genes and proteins in leukemogenesis and its potential as a therapeutic target in acute myeloid leukemia (AML). We explored the effects of velcrins, a class of small molecules able to modulate SLFN12 biological activity, on AML cells. Velcrin treatment of AML cells stabilized SLFN12 and promoted SLFN12 complex formation with phosphodiesterase 3A (PDE3A) or phosphodiesterase 3B (PDE3B). Such effects were associated with growth inhibitory and pro-apoptotic responses, as well as potent suppressive effects on leukemic cell growth. In addition, velcrin treatment suppressed clonogenic capacity of primitive leukemic progenitors and significantly extended survival in a mouse AML xenograft model. Taken together, these findings establish an important role of SLFN12 in leukemogenesis and raise the potential for the use of velcrins as a therapeutic strategy for AML.

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