The genomic landscape of core-binding factor acute myeloid leukemias

Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.

Chen, Xiang (author)
Gedman, Amanda Larson (author)
Boggs, Kristy (author)
Cheng, Jinjun (author)
Ma, Jing (author)
Radtke, Ina (author)
Chao, Jyh-Rong (author)
Walsh, Michael P (author)
Song, Guangchun (author)
Andersson, Anna KLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,St Jude Children´s Research Hospital, Memphis(Swepub:lu)kgen-aan (author)
Dang, Jinjun (author)
Dong, Li (author)
Liu, Yu (author)
Huether, Robert (author)
Cai, Zhongling (author)
Mulder, Heather (author)
Wu, Gang (author)
Edmonson, Michael (author)
Rusch, Michael (author)
Qu, Chunxu (author)
Li, Yongjin (author)
Vadodaria, Bhavin (author)
Wang, Jianmin (author)
Hedlund, Erin (author)
Cao, Xueyuan (author)
Yergeau, Donald (author)
Nakitandwe, Joy (author)
Pounds, Stanley B (author)
Shurtleff, Sheila (author)
Fulton, Robert S (author)
Fulton, Lucinda L (author)
Easton, John (author)
Parganas, Evan (author)
Pui, Ching-Hon (author)
Rubnitz, Jeffrey E (author)
Ding, Li (author)
Mardis, Elaine R (author)
Wilson, Richard K (author)
Gruber, Tanja A (author)
Mullighan, Charles G (author)
Schlenk, Richard F (author)
Paschka, Peter (author)
Döhner, Konstanze (author)
Döhner, Hartmut (author)
Bullinger, Lars (author)
Zhang, Jinghui (author)
Klco, Jeffery M (author)
Downing, James R (author)
Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin (creator_code:org_t)

In:Nature Genetics: Springer Science and Business Media LLC48, s. 1551-15561546-17181061-4036

By the author/editor: Faber, Zachary J; Chen, Xiang; Gedman, Amanda L ...; Boggs, Kristy; Cheng, Jinjun; Ma, Jing; show more...; Radtke, Ina; Chao, Jyh-Rong; Walsh, Michael P; Song, Guangchun; Andersson, Anna ...; Dang, Jinjun; Dong, Li; Liu, Yu; Huether, Robert; Cai, Zhongling; Mulder, Heather; Wu, Gang; Edmonson, Michae ...; Rusch, Michael; Qu, Chunxu; Li, Yongjin; Vadodaria, Bhavi ...; Wang, Jianmin; Hedlund, Erin; Cao, Xueyuan; Yergeau, Donald; Nakitandwe, Joy; Pounds, Stanley ...; Shurtleff, Sheil ...; Fulton, Robert S; Fulton, Lucinda ...; Easton, John; Parganas, Evan; Pui, Ching-Hon; Rubnitz, Jeffrey ...; Ding, Li; Mardis, Elaine R; Wilson, Richard ...; Gruber, Tanja A; Mullighan, Charl ...; Schlenk, Richard ...; Paschka, Peter; Döhner, Konstanz ...; Döhner, Hartmut; Bullinger, Lars; Zhang, Jinghui; Klco, Jeffery M; Downing, James R; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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