Cargando…

Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments

TP53 is a key tumor suppressor gene that plays an important role in regulating apoptosis, senescence, and DNA damage repair in response to cellular stress. Although somewhat rare, TP53-mutated AML has been identified as an important molecular subgroup with a prognosis that is arguably the worst of a...

Descripción completa

Detalles Bibliográficos
Autores principales: Granowicz, Eric M, Jonas, Brian A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037178/
https://www.ncbi.nlm.nih.gov/pubmed/35479302
http://dx.doi.org/10.2147/OTT.S265637
_version_ 1784693678105690112
author Granowicz, Eric M
Jonas, Brian A
author_facet Granowicz, Eric M
Jonas, Brian A
author_sort Granowicz, Eric M
collection PubMed
description TP53 is a key tumor suppressor gene that plays an important role in regulating apoptosis, senescence, and DNA damage repair in response to cellular stress. Although somewhat rare, TP53-mutated AML has been identified as an important molecular subgroup with a prognosis that is arguably the worst of any. Survival beyond one year is rare after induction chemotherapy with or without consolidative allogeneic stem cell transplant. Although response rates have been improved with hypomethylating agents, outcomes remain particularly poor due to short response duration. Improvements in our understanding of AML genetics and biology have led to a surge in novel treatment options, though the clinical applicability of these agents in TP53-mutated disease remains largely unknown. This review will focus on the epidemiology, molecular characteristics, and clinical significance of TP53 mutations in AML as well as emerging treatment options that are currently being studied.
format Online
Article
Text
id pubmed-9037178
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-90371782022-04-26 Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments Granowicz, Eric M Jonas, Brian A Onco Targets Ther Review TP53 is a key tumor suppressor gene that plays an important role in regulating apoptosis, senescence, and DNA damage repair in response to cellular stress. Although somewhat rare, TP53-mutated AML has been identified as an important molecular subgroup with a prognosis that is arguably the worst of any. Survival beyond one year is rare after induction chemotherapy with or without consolidative allogeneic stem cell transplant. Although response rates have been improved with hypomethylating agents, outcomes remain particularly poor due to short response duration. Improvements in our understanding of AML genetics and biology have led to a surge in novel treatment options, though the clinical applicability of these agents in TP53-mutated disease remains largely unknown. This review will focus on the epidemiology, molecular characteristics, and clinical significance of TP53 mutations in AML as well as emerging treatment options that are currently being studied. Dove 2022-04-21 /pmc/articles/PMC9037178/ /pubmed/35479302 http://dx.doi.org/10.2147/OTT.S265637 Text en © 2022 Granowicz and Jonas. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Granowicz, Eric M
Jonas, Brian A
Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments
title Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments
title_full Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments
title_fullStr Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments
title_full_unstemmed Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments
title_short Targeting TP53-Mutated Acute Myeloid Leukemia: Research and Clinical Developments
title_sort targeting tp53-mutated acute myeloid leukemia: research and clinical developments
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037178/
https://www.ncbi.nlm.nih.gov/pubmed/35479302
http://dx.doi.org/10.2147/OTT.S265637
work_keys_str_mv AT granowiczericm targetingtp53mutatedacutemyeloidleukemiaresearchandclinicaldevelopments
AT jonasbriana targetingtp53mutatedacutemyeloidleukemiaresearchandclinicaldevelopments