Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes

• Published in: Haematologica (Roma) Vol. 108; no. 2; pp. 522 - 531
• Main Authors: Fischer, Melissa A., Song, Yuanbin, Arrate, Maria P., Gbyli, Rana, Villaume, Matthew T., Smith, Brianna N., Childress, Merrida A., Stricker, Thomas P., Halene, Stephanie, Savona, Michael R.
• Format: Journal Article
• Language: English
• Published: Italy Fondazione Ferrata Storti 01.02.2023; Ferrata Storti Foundation
• Subjects: Animals; Apoptosis; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; Cell Line, Tumor; Disease Models, Animal; Leukemia, Myeloid, Acute - genetics; Mice; Myelodysplastic Syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - metabolism; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Proto-Oncogene Proteins c-bcl-2

Treatment for myelodysplastic syndromes (MDS) remains insufficient due to clonal heterogeneity and lack of effective clinical therapies. Dysregulation of apoptosis is observed across MDS subtypes regardless of mutations and represents an attractive therapeutic opportunity. Venetoclax (VEN), a select...