Bayesian multi-source regression and monocyte-associated gene expression predict BCL-2 inhibitor resistance in acute myeloid leukemia

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http://hdl.handle.net/10138/334423

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White , B S , Khan , S A , Mason , M J , Ammad-ud-din , M , Potdar , S , Malani , D , Kuusanmäki , H , Druker , B J , Heckman , C , Kallioniemi , O , Kurtz , S E , Porkka , K , Tognon , C E , Tyner , J W , Aittokallio , T , Wennerberg , K & Guinney , J 2021 , ' Bayesian multi-source regression and monocyte-associated gene expression predict BCL-2 inhibitor resistance in acute myeloid leukemia ' , npj precision oncology , vol. 5 , no. 1 , 71 . https://doi.org/10.1038/s41698-021-00209-9

Titel: Bayesian multi-source regression and monocyte-associated gene expression predict BCL-2 inhibitor resistance in acute myeloid leukemia
Författare: White, Brian S.; Khan, Suleiman A.; Mason, Mike J.; Ammad-ud-din, Muhammad; Potdar, Swapnil; Malani, Disha; Kuusanmäki, Heikki; Druker, Brian J.; Heckman, Caroline; Kallioniemi, Olli; Kurtz, Stephen E.; Porkka, Kimmo; Tognon, Cristina E.; Tyner, Jeffrey W.; Aittokallio, Tero; Wennerberg, Krister; Guinney, Justin
Upphovmannens organisation: Institute for Molecular Medicine Finland
Precision Systems Medicine
HUS Comprehensive Cancer Center
Department of Medicine
Digital Precision Cancer Medicine (iCAN)
Helsinki Institute for Information Technology
Tero Aittokallio / Principal Investigator
Bioinformatics
Krister Wennerberg / Principal Investigator
Datum: 2021-07-23
Språk: eng
Sidantal: 11
Tillhör serie: npj precision oncology
ISSN: 2397-768X
DOI: https://doi.org/10.1038/s41698-021-00209-9
Permanenta länken (URI): http://hdl.handle.net/10138/334423
Abstrakt: The FDA recently approved eight targeted therapies for acute myeloid leukemia (AML), including the BCL-2 inhibitor venetoclax. Maximizing efficacy of these treatments requires refining patient selection. To this end, we analyzed two recent AML studies profiling the gene expression and ex vivo drug response of primary patient samples. We find that ex vivo samples often exhibit a general sensitivity to (any) drug exposure, independent of drug target. We observe that this "general response across drugs" (GRD) is associated with FLT3-ITD mutations, clinical response to standard induction chemotherapy, and overall survival. Further, incorporating GRD into expression-based regression models trained on one of the studies improved their performance in predicting ex vivo response in the second study, thus signifying its relevance to precision oncology efforts. We find that venetoclax response is independent of GRD but instead show that it is linked to expression of monocyte-associated genes by developing and applying a multi-source Bayesian regression approach. The method shares information across studies to robustly identify biomarkers of drug response and is broadly applicable in integrative analyses.
Subject: DRUG RESPONSE CONSISTENCY
R PACKAGE
CANCER
SENSITIVITY
APOPTOSIS
CELLS
REGULARIZATION
IDENTIFICATION
INDUCTION
MECHANISM
3122 Cancers
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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