Amin Sobh, Elena Encinas, Alisha M Patel, Greeshma Surapaneni, Emilie Bonilla, Charlotte Leonie Kaestner, Janai Poullard, Monica Clerio, Karthik Vasan, Tzipporah Freeman, Dongwen Lv, Daphné Dupéré-Richer, Alberto Riva, Benjamin G Barwick, Daohong Zhou, Lawrence H Boise, Constantine S Mitsiades, Baek Kim, Richard L Bennett, Navdeep S Chandel, Jonathan D Licht
Chromosomal translocation (4;14), an adverse prognostic factor in multiple myeloma (MM), drives overexpression of the histone methyltransferase NSD2. A genome-wide CRISPR screen in MM cells identified adenylate kinase 2 (AK2), an enzyme critical for high energy phosphate transfer from the mitochondria, as an NSD2-driven vulnerability. AK2 suppression in t(4;14) MM cells decreased NADP(H) critical for conversion of ribonucleotides to deoxyribonucleosides, leading to replication stress, DNA damage and apoptosis...
April 10, 2024: Blood