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Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and predisposition to acute myeloid leukemia (AML). Stem cell genomic instability, microenvironmental aberrations, and somatic mutations cont...

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Autores principales: Lee, Paul, Yim, Rita, Yung, Yammy, Chu, Hiu-Tung, Yip, Pui-Kwan, Gill, Harinder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508686/
https://www.ncbi.nlm.nih.gov/pubmed/34638574
http://dx.doi.org/10.3390/ijms221910232
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author Lee, Paul
Yim, Rita
Yung, Yammy
Chu, Hiu-Tung
Yip, Pui-Kwan
Gill, Harinder
author_facet Lee, Paul
Yim, Rita
Yung, Yammy
Chu, Hiu-Tung
Yip, Pui-Kwan
Gill, Harinder
author_sort Lee, Paul
collection PubMed
description Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and predisposition to acute myeloid leukemia (AML). Stem cell genomic instability, microenvironmental aberrations, and somatic mutations contribute to leukemic transformation. The hypomethylating agents (HMAs), azacitidine and decitabine are the standard of care for patients with higher-risk MDS. Although these agents induce responses in up to 40–60% of patients, primary or secondary drug resistance is relatively common. To improve the treatment outcome, combinational therapies comprising HMA with targeted therapy or immunotherapy are being evaluated and are under continuous development. This review provides a comprehensive update of the molecular pathogenesis and immune-dysregulations involved in MDS, mechanisms of resistance to HMA, and strategies to overcome HMA resistance.
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spelling pubmed-85086862021-10-13 Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome Lee, Paul Yim, Rita Yung, Yammy Chu, Hiu-Tung Yip, Pui-Kwan Gill, Harinder Int J Mol Sci Review Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and predisposition to acute myeloid leukemia (AML). Stem cell genomic instability, microenvironmental aberrations, and somatic mutations contribute to leukemic transformation. The hypomethylating agents (HMAs), azacitidine and decitabine are the standard of care for patients with higher-risk MDS. Although these agents induce responses in up to 40–60% of patients, primary or secondary drug resistance is relatively common. To improve the treatment outcome, combinational therapies comprising HMA with targeted therapy or immunotherapy are being evaluated and are under continuous development. This review provides a comprehensive update of the molecular pathogenesis and immune-dysregulations involved in MDS, mechanisms of resistance to HMA, and strategies to overcome HMA resistance. MDPI 2021-09-23 /pmc/articles/PMC8508686/ /pubmed/34638574 http://dx.doi.org/10.3390/ijms221910232 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lee, Paul
Yim, Rita
Yung, Yammy
Chu, Hiu-Tung
Yip, Pui-Kwan
Gill, Harinder
Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome
title Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome
title_full Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome
title_fullStr Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome
title_full_unstemmed Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome
title_short Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome
title_sort molecular targeted therapy and immunotherapy for myelodysplastic syndrome
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508686/
https://www.ncbi.nlm.nih.gov/pubmed/34638574
http://dx.doi.org/10.3390/ijms221910232
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