TY - JOUR
T1 - Schlafen 12 modulation and targeting in acute myeloid leukemia
AU - Guillen Magaña, Jamie N
AU - Zannikou, Markella
AU - Baran, Aneta
AU - Small, Sara
AU - Schieber, Michael
AU - Schipma, Matthew J
AU - Bartom, Elizabeth T
AU - Kocherginsky, Masha
AU - Saleiro, Diana
AU - Beauchamp, Elspeth M
AU - Eckerdt, Frank
AU - Platanias, Leonidas C
PY - 2025/10/29
Y1 - 2025/10/29
N2 - 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.
AB - 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.
U2 - 10.1158/2767-9764.CRC-25-0283
DO - 10.1158/2767-9764.CRC-25-0283
M3 - Article
C2 - 41150877
SN - 2767-9764
JO - Cancer Research Communications
JF - Cancer Research Communications
ER -