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03.09.2024 | Progress in Hematology

Advances in pathogenesis research and challenges in treatment development for acute myeloid leukemia

verfasst von: Hiroki Yamaguchi

Erschienen in: International Journal of Hematology | Ausgabe 4/2024

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Abstract

Acute myeloid leukemia (AML) develops when hematopoietic stem cells acquire chromosomal and genetic abnormalities, transforming into leukemia stem cells (LSCs) and further gaining driver mutations. Advances in genomic analysis have identified numerous new gene mutations involved in AML development. Recent research has shown that individuals with germline mutations in genes like DDX41 and CEBPA develop AML upon acquiring additional somatic mutations, and the latest WHO classification separates AML with such mutations into distinct disease groups. LSCs are regulated by different metabolic processes than normal stem cells, contributing to drug resistance and relapse. LSCs rely on oxidative phosphorylation (OXPHOS) metabolism for energy production, and venetoclax inhibits this process, affecting LSCs. Resistant LSCs show enhanced glycolysis, which suggests that targeting both OXPHOS and glycolysis is crucial. While targeted therapies like FLT3, BCL-2, and IDH inhibitors have shown efficacy, resistance remains an issue, highlighting the need for new treatment strategies. CAR-T cell therapy is an emerging immunotherapy that shows particular promise for targeting CD123 and CLL-1, with acceptable toxicity. Future developments in CAR-T cell therapy and other immunotherapies are anticipated to improve AML treatment outcomes.
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Metadaten
Titel
Advances in pathogenesis research and challenges in treatment development for acute myeloid leukemia
verfasst von
Hiroki Yamaguchi
Publikationsdatum
03.09.2024
Verlag
Springer Nature Singapore
Erschienen in
International Journal of Hematology / Ausgabe 4/2024
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-024-03837-6

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