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Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription

Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recu...

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Autor principal: Beghini, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966602/
https://www.ncbi.nlm.nih.gov/pubmed/31817911
http://dx.doi.org/10.3390/cancers11121973
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author Beghini, Alessandro
author_facet Beghini, Alessandro
author_sort Beghini, Alessandro
collection PubMed
description Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBFβ-SMMHC) translocation product respectively, disrupt the essential hematopoietic function of the CBF. In the past decade, remarkable progress has been achieved in understanding the structure, three-dimensional (3D) chromosomal topology, and disease-inducing genetic and epigenetic abnormalities of the fusion proteins that arise from disruption of the CBF subunit alpha and beta genes. Although CBFLs have a relatively good prognosis compared to other leukemia subtypes, 40–50% of patients still relapse, requiring intensive chemotherapy and allogenic hematopoietic cell transplantation (alloHCT). To provide a rationale for the CBFL-associated altered hematopoietic development, in this review, we summarize the current understanding on the various molecular mechanisms, including dysregulation of Wnt/β-catenin signaling as an early event that triggers the translocations, playing a pivotal role in the pathophysiology of CBFL. Translation of these findings into the clinical setting is just beginning by improvement in risk stratification, MRD assessment, and development of targeted therapies.
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spelling pubmed-69666022020-02-04 Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription Beghini, Alessandro Cancers (Basel) Review Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBFβ-SMMHC) translocation product respectively, disrupt the essential hematopoietic function of the CBF. In the past decade, remarkable progress has been achieved in understanding the structure, three-dimensional (3D) chromosomal topology, and disease-inducing genetic and epigenetic abnormalities of the fusion proteins that arise from disruption of the CBF subunit alpha and beta genes. Although CBFLs have a relatively good prognosis compared to other leukemia subtypes, 40–50% of patients still relapse, requiring intensive chemotherapy and allogenic hematopoietic cell transplantation (alloHCT). To provide a rationale for the CBFL-associated altered hematopoietic development, in this review, we summarize the current understanding on the various molecular mechanisms, including dysregulation of Wnt/β-catenin signaling as an early event that triggers the translocations, playing a pivotal role in the pathophysiology of CBFL. Translation of these findings into the clinical setting is just beginning by improvement in risk stratification, MRD assessment, and development of targeted therapies. MDPI 2019-12-07 /pmc/articles/PMC6966602/ /pubmed/31817911 http://dx.doi.org/10.3390/cancers11121973 Text en © 2019 by the author. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Beghini, Alessandro
Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription
title Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription
title_full Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription
title_fullStr Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription
title_full_unstemmed Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription
title_short Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription
title_sort core binding factor leukemia: chromatin remodeling moves towards oncogenic transcription
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966602/
https://www.ncbi.nlm.nih.gov/pubmed/31817911
http://dx.doi.org/10.3390/cancers11121973
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