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Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia
BACKGROUND: The ZBTB16‐RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor‐α (RARA) rearrangements. A...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209618/ https://www.ncbi.nlm.nih.gov/pubmed/34042280 http://dx.doi.org/10.1002/cam4.3904 |
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author | Fabiani, Emiliano Cicconi, Laura Nardozza, Anna Maria Cristiano, Antonio Rossi, Marianna Ottone, Tiziana Falconi, Giulia Divona, Mariadomenica Testi, Anna Maria Annibali, Ombretta Castelli, Roberto Lazarevic, Vladimir Rego, Eduardo Montesinos, Pau Esteve, Jordi Venditti, Adriano Della Porta, Matteo Arcese, William Lo‐Coco, Francesco Voso, Maria Teresa |
author_facet | Fabiani, Emiliano Cicconi, Laura Nardozza, Anna Maria Cristiano, Antonio Rossi, Marianna Ottone, Tiziana Falconi, Giulia Divona, Mariadomenica Testi, Anna Maria Annibali, Ombretta Castelli, Roberto Lazarevic, Vladimir Rego, Eduardo Montesinos, Pau Esteve, Jordi Venditti, Adriano Della Porta, Matteo Arcese, William Lo‐Coco, Francesco Voso, Maria Teresa |
author_sort | Fabiani, Emiliano |
collection | PubMed |
description | BACKGROUND: The ZBTB16‐RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor‐α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to all‐trans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis. AIMS: The mutational profile of ZBTB16‐RARA rearranged AML has not been described so far. MATERIALS AND METHODS: We performed targeted next‐generation sequencing of 24 myeloid genes in BM diagnostic samples from seven ZBTB16‐RARA+AML, 103 non‐RARA rearranged AML, and 46 APL. The seven ZBTB16‐RARA‐positive patients were then screened for additional mutations using whole exome sequencing (n = 3) or an extended cancer panel including 409 genes (n = 4). RESULTS: ZBTB16‐RARA+AML showed an intermediate number of mutations per patient and involvement of different genes, as compared to APL and other AMLs. In particular, we found a high incidence of ARID1A mutations in ZBTB16‐RARA+AML (five of seven cases, 71%). Mutations in ARID2 and SMARCA4, other tumor suppressor genes also belonging to SWI/SNF chromatin remodeling complexes, were also identified in one case (14%). DISCUSSION AND CONCLUSION: Our data suggest the association of mutations of the ARID1A gene and of the other members of the SWI/SNF chromatin remodeling complexes with ZBTB16‐RARA+AMLs, where they may support the peculiar disease phenotype. |
format | Online Article Text |
id | pubmed-8209618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82096182021-06-25 Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia Fabiani, Emiliano Cicconi, Laura Nardozza, Anna Maria Cristiano, Antonio Rossi, Marianna Ottone, Tiziana Falconi, Giulia Divona, Mariadomenica Testi, Anna Maria Annibali, Ombretta Castelli, Roberto Lazarevic, Vladimir Rego, Eduardo Montesinos, Pau Esteve, Jordi Venditti, Adriano Della Porta, Matteo Arcese, William Lo‐Coco, Francesco Voso, Maria Teresa Cancer Med Clinical Cancer Research BACKGROUND: The ZBTB16‐RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor‐α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to all‐trans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis. AIMS: The mutational profile of ZBTB16‐RARA rearranged AML has not been described so far. MATERIALS AND METHODS: We performed targeted next‐generation sequencing of 24 myeloid genes in BM diagnostic samples from seven ZBTB16‐RARA+AML, 103 non‐RARA rearranged AML, and 46 APL. The seven ZBTB16‐RARA‐positive patients were then screened for additional mutations using whole exome sequencing (n = 3) or an extended cancer panel including 409 genes (n = 4). RESULTS: ZBTB16‐RARA+AML showed an intermediate number of mutations per patient and involvement of different genes, as compared to APL and other AMLs. In particular, we found a high incidence of ARID1A mutations in ZBTB16‐RARA+AML (five of seven cases, 71%). Mutations in ARID2 and SMARCA4, other tumor suppressor genes also belonging to SWI/SNF chromatin remodeling complexes, were also identified in one case (14%). DISCUSSION AND CONCLUSION: Our data suggest the association of mutations of the ARID1A gene and of the other members of the SWI/SNF chromatin remodeling complexes with ZBTB16‐RARA+AMLs, where they may support the peculiar disease phenotype. John Wiley and Sons Inc. 2021-05-27 /pmc/articles/PMC8209618/ /pubmed/34042280 http://dx.doi.org/10.1002/cam4.3904 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Cancer Research Fabiani, Emiliano Cicconi, Laura Nardozza, Anna Maria Cristiano, Antonio Rossi, Marianna Ottone, Tiziana Falconi, Giulia Divona, Mariadomenica Testi, Anna Maria Annibali, Ombretta Castelli, Roberto Lazarevic, Vladimir Rego, Eduardo Montesinos, Pau Esteve, Jordi Venditti, Adriano Della Porta, Matteo Arcese, William Lo‐Coco, Francesco Voso, Maria Teresa Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia |
title | Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia |
title_full | Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia |
title_fullStr | Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia |
title_full_unstemmed | Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia |
title_short | Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia |
title_sort | mutational profile of zbtb16‐rara‐positive acute myeloid leukemia |
topic | Clinical Cancer Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209618/ https://www.ncbi.nlm.nih.gov/pubmed/34042280 http://dx.doi.org/10.1002/cam4.3904 |
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