ArticleHaematologica2025
Lysosomal acid lipase A modulates leukemia stem cell response to venetoclax/tyrosine kinase inhibitor combination therapy in blast phase chronic myeloid leukemia.
Article in Haematologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Single-cell RNA sequencing and Mendelian randomization identify context-dependent LIPA-associated classical monocyte states in sepsis and breast cancer.Breast cancer research and treatment · 2026Article
- The tumor microenvironment in leukemia: molecular pathways of immune evasion.Frontiers in immunology · 2026Review
- BCR::ABL1 expression in chronic myeloid leukemia cells in low oxygen is regulated by glutamine via CD36-mediated fatty acid uptake.Cancer cell international · 2025Article
- LIPA-frogging blast phase chronic myeloid leukemia: hopping over resistance with lysosomal targeting.Haematologica · 2025Article
- Drug clinical trial landscape of chronic myeloid leukemia: achieving the endpoint or continuing the journey?Journal of translational medicine · 2024Article
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
The treatment of blast phase chronic myeloid leukemia (bpCML) remains a challenge due, at least in part, to drug resistance of leukemia stem cells (LSC). Recent clinical evidence suggests that the BCL-2 inhibitor venetoclax in combination with ABL-targeting tyrosine kinase inhibitors can eradicate bpCML LSC. In this study, we employed preclinical models of bpCML to investigate the efficacy and underlying mechanism of LSC-targeting with combinations of venetoclax/tyrosine kinase inhibitors. Transcriptional analysis of LSC exposed to venetoclax and dasatinib revealed upregulation of genes involved in lysosomal biology, in particular lysosomal acid lipase A (LIPA), a regulator of free fatty acids. Metabolomic analysis confirmed increased levels of free fatty acids in response to treatment with venetoclax/dasatinib. Pretreatment of leukemia cells with bafilomycin, a specific lysosome inhibitor, or genetic perturbation of LIPA, resulted in increased sensitivity of leukemia cells to venetoclax/dasatinib, implicating LIPA in treatment resistance. Importantly, venetoclax/dasatinib treatment did not affect normal stem cell function, suggesting a leukemia-specific response. These results demonstrate that venetoclax/dasatinib is a LSC-selective regimen in bpCML and that disrupting LIPA and fatty acid transport enhances the response to venetoclax/ dasatinib when targeting LSC, providing a rationale for exploring lysosomal disruption as an adjunctive therapeutic strategy to prolong disease remission.
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Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.