Harnessing ALDH1A2 vulnerability in T-cell acute lymphoblastic leukemia
Andrieu, G. P.; Courtois, L.; Bonnet, M.; Gillet, C.; Queri, M.; Feroul, M.; Lhermitte, L.; Villarese, P.; Cabannes-Hamy, A.; Rousselot, P.; Perez, M.; Ceylan, I.; Spicuglia, S.; Asnafi, V.
Show abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with limited therapeutic options, particularly in the relapsed/refractory (R/R) setting. Unlike other hematological malignancies, which benefit from targeted immunotherapies, T-ALL remains reliant on chemotherapy, leading to poor outcomes in R/R cases. Identifying novel therapeutic vulnerabilities is crucial to improving the outcomes of patients. Herein, we identify aldehyde dehydrogenase 1A2 (ALDH1A2) as a T-ALL-specific enzyme essential for leukemic cell survival. Transcriptomic and epigenetic analyses reveal its selective expression, regulated by the TAL1 oncogene. Pharmacological inhibition of ALDH1A2 using Dimate demonstrates potent anti-leukemic activity across diverse T-ALL subtypes, including primary samples of relapsed disease. These findings establish ALDH1A2 as a therapeutic target in T-ALL and support ALDH inhibition as a promising strategy to overcome drug resistance and improve treatment outcomes in R/R T-ALL.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Resistance mechanism to Notch inhibition and combination therapy in human T cell acute lymphoblastic leukemia 97%
- Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities 97%
- ATP citrate lyase is an essential player of the metabolic rewiring induced by PTEN loss during T-ALL development. 96%
Similar papers in this journal
- Ex Vivo Drug Responses and Molecular Profiles of 597 Pediatric Acute Lymphoblastic Leukemia Patients 96%
- Linker histone H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape 96%
- NOTCH1 fusions in pediatric T-cell lymphoblastic lymphoma: a high-risk subgroup with CCL17 (TARC) levels as diagnostic biomarker 94%
Similar papers in this journal
- Combining LSD1 and JAK-STAT inhibition targets Down syndrome-associated myeloid leukemia at its core 96%
- Base edited "universal" donor CAR T cell strategies for acute myeloid leukaemia 95%
- Resistance to decitabine and 5-azacytidine emerges from adaptive responses of the pyrimidine metabolism network 95%
Similar papers in this journal
- Genome-wide CRISPR Screens Identify Ferroptosis as a Novel Therapeutic Vulnerability in Acute Lymphoblastic Leukemia 96%
- Inducing synthetic lethality for selective targeting of acute myeloid leukemia cells harboring STAG2 mutations 94%
- Aberrant MNX1 Expression Associated with t(7;12)(q36;p13) Pediatric Acute Myeloid 1 Leukemia Induces the Disease Through Altering Histone Methylation 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.