Mapping the proteogenomic landscape enables prediction of drug response in acute myeloid leukemia
Year: 2024
Type: article
Study design: Observational Study
Abstract: Acute myeloid leukemia is a poor-prognosis cancer commonly stratified by genetic aberrations, but these mutations are often heterogeneous and fail to consistently predict therapeutic response. Here, we combine transcriptomic, proteomic, and phosphoproteomic datasets with ex vivo drug sensitivity data to help understand the underlying pathophysiology of AML beyond mutations. We measure the proteome and phosphoproteome of 210 patients and combine them with genomic and transcriptomic measurements to identify four proteogenomic subtypes that complement existing genetic subtypes. We build a predictor to classify samples into subtypes and map them to a "landscape" that identifies specific drug response patterns. We then build a drug response prediction model to identify drugs that target distinct subtypes and validate our findings on cell lines representing various stages of quizartinib resistance. Our results show how multiomics data together with drug sensitivity data can inform therapy stratification and drug combinations in AML.
Source: Cell Reports Medicine
Authors: James C. Pino, Camilo Posso, Sunil K. Joshi, Michael Nestor, Jamie Moon, Joshua R. Hansen, Chelsea Hutchinson-Bunch, Marina A. Gritsenko, Karl K. Weitz, Kevin Watanabe-Smith, Nicola Long, Jason E. McDermott, Brian J. Druker, Tao Liu, Jeffrey W. Tyner, Anupriya Agarwal, Elie Traer, Paul D. Piehowski, Cristina E. Tognon, Karin D. Rodland, Sara J.C. Gosline
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,460
Awards: G125460123, G138090931, G1899721271, G2506945562, G2510423872, G2988778103, G3437276931, G391136020, G5321382714, G5726405315, G6582107015, Defining the stromal landscape that sustains AML drug resistance, G7064300592, G8275864181, G835082186, Mechanisms and targeting of inflammatory cytokine-driven expansion and progression in AML, G8574172138, Proteogenomic characterization of early and late resistance mechanisms in acute myeloid leukemia
OpenAlex ID: W4390921274