ArticleBlood advances2022
Associating drug sensitivity with differentiation status identifies effective combinations for acute myeloid leukemia.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 16 citations in OpenAlex.
- m6A and NuRD complexes regulate monocytic differentiation and resistance to BCL2/BCL2L1 inhibitors in acute myeloid leukemia.Haematologica · 2026Article
- A Rho GTPase-related gene signature predicts prognosis and reveals an immunosuppressive microenvironment in lung adenocarcinoma: an integrated analysis of bulk and single-cell RNA sequencing data.Scientific reports · 2026Article
- Pathomic model to predict the expression of UQCRH and overall survival of lung adenocarcinoma patients.Diagnostic pathology · 2026Article
- CDK4/6 inhibition overcomes venetoclax resistance mechanisms with enhanced combination activity in acute myeloid leukemia.Cell reports. Medicine · 2026Article
- Deciphering Multitarget Mechanisms of Cardiac Glycosides in Acute Myeloid Leukemia Using a Network Pharmacology and Molecular Docking.Drug design, development and therapy · 2026Article
- ASAH1-mediated sphingolipid metabolic reprogramming in venetoclax resistance of AML: beyond the monocytic phenotypes.BMC cancer · 2025Article
- Article
- MutantProceedings of the National Academy of Sciences of the United States of America · 2025Article
- scPharm: Identifying Pharmacological Subpopulations of Single Cells for Precision Medicine in Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A lncRNA signature associated with endoplasmic reticulum stress supports prognostication and prediction of drug resistance in acute myelogenous leukemia.Translational cancer research · 2024Article
- Article
- Impact of monocytic differentiation on acute myeloid leukemia patients treated with venetoclax and hypomethylating agents.Cancer medicine · 2024Article
- Venetoclax Resistance in Acute Myeloid Leukemia.Cancers · 2024Review
- Mapping the proteogenomic landscape enables prediction of drug response in acute myeloid leukemia.Cell reports. Medicine · 2024Article
- ATP1A1/BCL2L1 predicts the response of myelomonocytic and monocytic acute myeloid leukemia to cardiac glycosides.Leukemia · 2024Article
- Article
- Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Using ex vivo drug screening of primary patient specimens, we identified the combination of the p38 MAPK inhibitor doramapimod (DORA) with the BCL2 inhibitor venetoclax (VEN) as demonstrating broad, enhanced efficacy compared with each single agent across 335 acute myeloid leukemia (AML) patient samples while sparing primary stromal cells. Single-agent DORA and VEN sensitivity was associated with distinct, nonoverlapping tumor cell differentiation states. In particular, increased monocytes, M4/M5 French-American-British classification, and CD14+ immunophenotype tracked with sensitivity to DORA and resistance to VEN but were mitigated with the combination. Increased expression of MAPK14 and BCL2, the respective primary targets of DORA and VEN, were observed in monocytic and undifferentiated leukemias, respectively. Enrichment for DORA and VEN sensitivities was observed in AML with monocyte-like and progenitor-like transcriptomic signatures, respectively, and these associations diminished with the combination. The mechanism underlying the combination's enhanced efficacy may result from inhibition of p38 MAPK-mediated phosphorylation of BCL2, which in turn enhances sensitivity to VEN. These findings suggest exploiting complementary drug sensitivity profiles with respect to leukemic differentiation state, such as dual targeting of p38 MAPK and BCL2, offers opportunity for broad, enhanced efficacy across the clinically challenging heterogeneous landscape of AML.
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