Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives

Abstract Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somati...

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Main Authors: Zahra Khosroabadi, Samaneh Azaryar, Hassan Dianat-Moghadam, Zohreh Amoozgar, Mohammadreza Sharifi
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Molecular Medicine
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Online Access:https://doi.org/10.1186/s10020-025-01085-w
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author Zahra Khosroabadi
Samaneh Azaryar
Hassan Dianat-Moghadam
Zohreh Amoozgar
Mohammadreza Sharifi
author_facet Zahra Khosroabadi
Samaneh Azaryar
Hassan Dianat-Moghadam
Zohreh Amoozgar
Mohammadreza Sharifi
author_sort Zahra Khosroabadi
collection DOAJ
description Abstract Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment. ScRNA-seq allows the identification of quiescent stem-like cells, and leukemia stem cells responsible for resistance to therapeutic approaches and relapse after treatment. This method also introduces the factors and mechanisms that enhance the efficacy of the HSCT process. Generated data of the transcriptional profile of the AML could even allow the development of cancer vaccines and CAR T-cell therapies while saving valuable time and alleviating dangerous side effects of chemotherapy and HSCT in vivo. However, scRNA-seq applications face various challenges such as a large amount of data for high-dimensional analysis, technical noise, batch effects, and finding small biological patterns, which could be improved in combination with artificial intelligence models.
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issn 1528-3658
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publishDate 2025-01-01
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spelling doaj-art-b4fbe941b1034e7381528b2a294ca5e52025-02-02T12:29:25ZengBMCMolecular Medicine1528-36582025-01-0131112610.1186/s10020-025-01085-wSingle cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectivesZahra Khosroabadi0Samaneh Azaryar1Hassan Dianat-Moghadam2Zohreh Amoozgar3Mohammadreza Sharifi4Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical SchoolDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesAbstract Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment. ScRNA-seq allows the identification of quiescent stem-like cells, and leukemia stem cells responsible for resistance to therapeutic approaches and relapse after treatment. This method also introduces the factors and mechanisms that enhance the efficacy of the HSCT process. Generated data of the transcriptional profile of the AML could even allow the development of cancer vaccines and CAR T-cell therapies while saving valuable time and alleviating dangerous side effects of chemotherapy and HSCT in vivo. However, scRNA-seq applications face various challenges such as a large amount of data for high-dimensional analysis, technical noise, batch effects, and finding small biological patterns, which could be improved in combination with artificial intelligence models.https://doi.org/10.1186/s10020-025-01085-wAI modelAMLDrug resistanceSingle cell RNA sequencingTumor heterogeneity
spellingShingle Zahra Khosroabadi
Samaneh Azaryar
Hassan Dianat-Moghadam
Zohreh Amoozgar
Mohammadreza Sharifi
Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives
Molecular Medicine
AI model
AML
Drug resistance
Single cell RNA sequencing
Tumor heterogeneity
title Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives
title_full Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives
title_fullStr Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives
title_full_unstemmed Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives
title_short Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives
title_sort single cell rna sequencing improves the next generation of approaches to aml treatment challenges and perspectives
topic AI model
AML
Drug resistance
Single cell RNA sequencing
Tumor heterogeneity
url https://doi.org/10.1186/s10020-025-01085-w
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AT hassandianatmoghadam singlecellrnasequencingimprovesthenextgenerationofapproachestoamltreatmentchallengesandperspectives
AT zohrehamoozgar singlecellrnasequencingimprovesthenextgenerationofapproachestoamltreatmentchallengesandperspectives
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