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Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience

Acute promyelocytic leukemia (APL) pathogenesis is based on RARA gene translocations, which are of high importance in the diagnosis of and proper therapy selection for APL. However, in some cases acute myeloid leukemia (AML) demonstrates APL-like morphological features such as atypical promyelocytes...

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Autores principales: Borkovskaia, Aleksandra, Bogacheva, Sofia, Konyukhova, Tatiana, Dadakhanova, Elina, Gaskova, Marina, Soldatkina, Olga, Dubrovina, Maria, Popov, Alexander, Mikhailova, Ekaterina, Inushkina, Evgenia, Kazanov, Marat, Matveev, Evgeniy, Novichkova, Galina, Maschan, Michael, Maschan, Alexey, Olshanskaya, Yulia, Zerkalenkova, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048084/
https://www.ncbi.nlm.nih.gov/pubmed/36980947
http://dx.doi.org/10.3390/genes14030675
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author Borkovskaia, Aleksandra
Bogacheva, Sofia
Konyukhova, Tatiana
Dadakhanova, Elina
Gaskova, Marina
Soldatkina, Olga
Dubrovina, Maria
Popov, Alexander
Mikhailova, Ekaterina
Inushkina, Evgenia
Kazanov, Marat
Matveev, Evgeniy
Novichkova, Galina
Maschan, Michael
Maschan, Alexey
Olshanskaya, Yulia
Zerkalenkova, Elena
author_facet Borkovskaia, Aleksandra
Bogacheva, Sofia
Konyukhova, Tatiana
Dadakhanova, Elina
Gaskova, Marina
Soldatkina, Olga
Dubrovina, Maria
Popov, Alexander
Mikhailova, Ekaterina
Inushkina, Evgenia
Kazanov, Marat
Matveev, Evgeniy
Novichkova, Galina
Maschan, Michael
Maschan, Alexey
Olshanskaya, Yulia
Zerkalenkova, Elena
author_sort Borkovskaia, Aleksandra
collection PubMed
description Acute promyelocytic leukemia (APL) pathogenesis is based on RARA gene translocations, which are of high importance in the diagnosis of and proper therapy selection for APL. However, in some cases acute myeloid leukemia (AML) demonstrates APL-like morphological features such as atypical promyelocytes accumulation. This type of AML is characterized by the involvement of other RAR family members or completely different genes. In the present study, we used conventional karyotyping, FISH and high-throughput sequencing in a group of 271 de novo AML with atypical promyelocytes accumulation. Of those, 255 cases were shown to carry a typical chromosomal translocation t(15;17)(q24;q21) with PML::RARA chimeric gene formation (94.1%). Other RARA-positive cases exhibited cryptic PML::RARA fusion without t(15;17)(q24;q21) (1.8%, n = 5) and variant t(5;17)(q35;q21) translocation with NPM1::RARA chimeric gene formation (1.5%, n = 4). However, 7 RARA-negative AMLs with atypical promyelocytes accumulation were also discovered. These cases exhibited TBL1XR1::RARB and KMT2A::SEPT6 fusions as well as mutations, e.g., NPM1 insertion and non-recurrent chromosomal aberrations. Our findings demonstrate the genetic diversity of AML with APL-like morphological features, which is of high importance for successful therapy implementation.
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spelling pubmed-100480842023-03-29 Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience Borkovskaia, Aleksandra Bogacheva, Sofia Konyukhova, Tatiana Dadakhanova, Elina Gaskova, Marina Soldatkina, Olga Dubrovina, Maria Popov, Alexander Mikhailova, Ekaterina Inushkina, Evgenia Kazanov, Marat Matveev, Evgeniy Novichkova, Galina Maschan, Michael Maschan, Alexey Olshanskaya, Yulia Zerkalenkova, Elena Genes (Basel) Article Acute promyelocytic leukemia (APL) pathogenesis is based on RARA gene translocations, which are of high importance in the diagnosis of and proper therapy selection for APL. However, in some cases acute myeloid leukemia (AML) demonstrates APL-like morphological features such as atypical promyelocytes accumulation. This type of AML is characterized by the involvement of other RAR family members or completely different genes. In the present study, we used conventional karyotyping, FISH and high-throughput sequencing in a group of 271 de novo AML with atypical promyelocytes accumulation. Of those, 255 cases were shown to carry a typical chromosomal translocation t(15;17)(q24;q21) with PML::RARA chimeric gene formation (94.1%). Other RARA-positive cases exhibited cryptic PML::RARA fusion without t(15;17)(q24;q21) (1.8%, n = 5) and variant t(5;17)(q35;q21) translocation with NPM1::RARA chimeric gene formation (1.5%, n = 4). However, 7 RARA-negative AMLs with atypical promyelocytes accumulation were also discovered. These cases exhibited TBL1XR1::RARB and KMT2A::SEPT6 fusions as well as mutations, e.g., NPM1 insertion and non-recurrent chromosomal aberrations. Our findings demonstrate the genetic diversity of AML with APL-like morphological features, which is of high importance for successful therapy implementation. MDPI 2023-03-08 /pmc/articles/PMC10048084/ /pubmed/36980947 http://dx.doi.org/10.3390/genes14030675 Text en © 2023 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 Article
Borkovskaia, Aleksandra
Bogacheva, Sofia
Konyukhova, Tatiana
Dadakhanova, Elina
Gaskova, Marina
Soldatkina, Olga
Dubrovina, Maria
Popov, Alexander
Mikhailova, Ekaterina
Inushkina, Evgenia
Kazanov, Marat
Matveev, Evgeniy
Novichkova, Galina
Maschan, Michael
Maschan, Alexey
Olshanskaya, Yulia
Zerkalenkova, Elena
Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience
title Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience
title_full Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience
title_fullStr Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience
title_full_unstemmed Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience
title_short Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience
title_sort molecular heterogeneity of pediatric aml with atypical promyelocytes accumulation in children—a single center experience
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048084/
https://www.ncbi.nlm.nih.gov/pubmed/36980947
http://dx.doi.org/10.3390/genes14030675
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