MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199

• Published in: Cell reports (Cambridge) Vol. 13; no. 12; pp. 2715 - 2727
• Main Authors: Benito, Juliana M., Godfrey, Laura, Kojima, Kensuke, Hogdal, Leah, Wunderlich, Mark, Geng, Huimin, Marzo, Isabel, Harutyunyan, Karine G., Golfman, Leonard, North, Phillip, Kerry, Jon, Ballabio, Erica, Chonghaile, Triona Ní, Gonzalo, Oscar, Qiu, Yihua, Jeremias, Irmela, Debose, LaKiesha, O’Brien, Eric, Ma, Helen, Zhou, Ping, Jacamo, Rodrigo, Park, Eugene, Coombes, Kevin R., Zhang, Nianxiang, Thomas, Deborah A., O’Brien, Susan, Kantarjian, Hagop M., Leverson, Joel D., Kornblau, Steven M., Andreeff, Michael, Müschen, Markus, Zweidler-McKay, Patrick A., Mulloy, James C., Letai, Anthony, Milne, Thomas A., Konopleva, Marina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.12.2015; Cell Press; Elsevier
• Subjects: Animals; apoptosis pathways; bcl-2 family members; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Cell Line, Tumor; DOT1L; Genes, bcl-2; H3K79 methylation; Histone-Lysine N-Methyltransferase - genetics; Humans; leukemias; Methylation; Mice; Mice, Inbred NOD; Mice, SCID; MLL/AF4; Myeloid-Lymphoid Leukemia Protein - genetics; Myeloid-Lymphoid Leukemia Protein - metabolism; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Sulfonamides - pharmacology; MLL/AF4; apoptosis pathways; bcl-2 family members; leukemias; H3K79 methylation; DOT1L

Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocat...