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Targeted Therapy in Acute Lymphoblastic Leukaemia
The last decade has seen a significant leap in our understanding of the wide range of genetic lesions underpinning acute lymphoblastic leukaemia (ALL). Next generation sequencing has led to the identification of driver mutations with significant implications on prognosis and has defined entities suc...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398498/ https://www.ncbi.nlm.nih.gov/pubmed/34442359 http://dx.doi.org/10.3390/jpm11080715 |
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author | Salvaris, Ross Fedele, Pasquale Luke |
author_facet | Salvaris, Ross Fedele, Pasquale Luke |
author_sort | Salvaris, Ross |
collection | PubMed |
description | The last decade has seen a significant leap in our understanding of the wide range of genetic lesions underpinning acute lymphoblastic leukaemia (ALL). Next generation sequencing has led to the identification of driver mutations with significant implications on prognosis and has defined entities such as BCR-ABL-like ALL, where targeted therapies such as tyrosine kinase inhibitors (TKIs) and JAK inhibitors may play a role in its treatment. In Philadelphia positive ALL, the introduction of TKIs into frontline treatment regimens has already transformed patient outcomes. In B-ALL, agents targeting surface receptors CD19, CD20 and CD22, including monoclonal antibodies, bispecific T cell engagers, antibody drug conjugates and chimeric antigen receptor (CAR) T cells, have shown significant activity but come with unique toxicities and have implications for how treatment is sequenced. Advances in T-ALL have lagged behind those seen in B-ALL. However, agents such as nelarabine, bortezomib and CAR T cell therapy targeting T cell antigens have been examined with promising results seen. As our understanding of disease biology in ALL grows, as does our ability to target pathways such as apoptosis, through BH3 mimetics, chemokines and epigenetic regulators. This review aims to highlight a range of available and emerging targeted therapeutics in ALL, to explore their mechanisms of action and to discuss the current evidence for their use. |
format | Online Article Text |
id | pubmed-8398498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83984982021-08-29 Targeted Therapy in Acute Lymphoblastic Leukaemia Salvaris, Ross Fedele, Pasquale Luke J Pers Med Review The last decade has seen a significant leap in our understanding of the wide range of genetic lesions underpinning acute lymphoblastic leukaemia (ALL). Next generation sequencing has led to the identification of driver mutations with significant implications on prognosis and has defined entities such as BCR-ABL-like ALL, where targeted therapies such as tyrosine kinase inhibitors (TKIs) and JAK inhibitors may play a role in its treatment. In Philadelphia positive ALL, the introduction of TKIs into frontline treatment regimens has already transformed patient outcomes. In B-ALL, agents targeting surface receptors CD19, CD20 and CD22, including monoclonal antibodies, bispecific T cell engagers, antibody drug conjugates and chimeric antigen receptor (CAR) T cells, have shown significant activity but come with unique toxicities and have implications for how treatment is sequenced. Advances in T-ALL have lagged behind those seen in B-ALL. However, agents such as nelarabine, bortezomib and CAR T cell therapy targeting T cell antigens have been examined with promising results seen. As our understanding of disease biology in ALL grows, as does our ability to target pathways such as apoptosis, through BH3 mimetics, chemokines and epigenetic regulators. This review aims to highlight a range of available and emerging targeted therapeutics in ALL, to explore their mechanisms of action and to discuss the current evidence for their use. MDPI 2021-07-25 /pmc/articles/PMC8398498/ /pubmed/34442359 http://dx.doi.org/10.3390/jpm11080715 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 Salvaris, Ross Fedele, Pasquale Luke Targeted Therapy in Acute Lymphoblastic Leukaemia |
title | Targeted Therapy in Acute Lymphoblastic Leukaemia |
title_full | Targeted Therapy in Acute Lymphoblastic Leukaemia |
title_fullStr | Targeted Therapy in Acute Lymphoblastic Leukaemia |
title_full_unstemmed | Targeted Therapy in Acute Lymphoblastic Leukaemia |
title_short | Targeted Therapy in Acute Lymphoblastic Leukaemia |
title_sort | targeted therapy in acute lymphoblastic leukaemia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398498/ https://www.ncbi.nlm.nih.gov/pubmed/34442359 http://dx.doi.org/10.3390/jpm11080715 |
work_keys_str_mv | AT salvarisross targetedtherapyinacutelymphoblasticleukaemia AT fedelepasqualeluke targetedtherapyinacutelymphoblasticleukaemia |