A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Bayesian multi-source regression and monocyte-associated gene expression predict BCL-2 inhibitor resistance in acute myeloid leukemia
Tekijät: 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
Kustantaja: NATURE RESEARCH
Julkaisuvuosi: 2021
Journal: npj Precision Oncology
Tietokannassa oleva lehden nimi: NPJ PRECISION ONCOLOGY
Lehden akronyymi: NPJ PRECIS ONCOL
Artikkelin numero: ARTN 71
Vuosikerta: 5
Sivujen määrä: 11
eISSN: 2397-768X
DOI: https://doi.org/10.1038/s41698-021-00209-9
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/66909018
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
