Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia
Abstract 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) rearrange...
Main Authors: | , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-06-01
|
Series: | Cancer Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1002/cam4.3904 |
id |
doaj-65f7159aca3f488c9a7bad0da0d53eea |
---|---|
record_format |
Article |
spelling |
doaj-65f7159aca3f488c9a7bad0da0d53eea2021-06-17T09:30:44ZengWileyCancer Medicine2045-76342021-06-0110123839384710.1002/cam4.3904Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemiaEmiliano Fabiani0Laura Cicconi1Anna Maria Nardozza2Antonio Cristiano3Marianna Rossi4Tiziana Ottone5Giulia Falconi6Mariadomenica Divona7Anna Maria Testi8Ombretta Annibali9Roberto Castelli10Vladimir Lazarevic11Eduardo Rego12Pau Montesinos13Jordi Esteve14Adriano Venditti15Matteo Della Porta16William Arcese17Francesco Lo‐Coco18Maria Teresa Voso19Department of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyUnit of Hematology Santo Spirito Hospital Rome ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyCancer Center ‐ IRCCS Humanitas Clinical & Research Hospital and Humanitas University Milan ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyDepartment of Translational and Precision Medicine and Hematology Sapienza University Rome ItalyHematology and Stem Cell Transplantation Unit University Campus Biomedico Rome ItalyDepartment of Biomedical and Clinical Sciences Luigi Sacco Hospital Milan ItalyDepartment of Hematology, Oncology and Radiation Physics Skåne University Hospital Lund SwedenDepartment of Internal Medicine Medical School of Ribeirao Preto Sau Paulo BrazilHematology Department Hospital Universitari i Politècnico la Fe Valencia SpainDepartment of Hematology Hospital Clínic de Barcelona Barcelona SpainDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyCancer Center ‐ IRCCS Humanitas Clinical & Research Hospital and Humanitas University Milan ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyDepartment of Biomedicine and Prevention University Tor Vergata Rome Rome ItalyAbstract 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.https://doi.org/10.1002/cam4.3904AMLARID1ANGSZBTB16‐RARA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emiliano Fabiani Laura Cicconi Anna Maria Nardozza Antonio Cristiano Marianna Rossi Tiziana Ottone Giulia Falconi Mariadomenica Divona Anna Maria Testi Ombretta Annibali Roberto Castelli Vladimir Lazarevic Eduardo Rego Pau Montesinos Jordi Esteve Adriano Venditti Matteo Della Porta William Arcese Francesco Lo‐Coco Maria Teresa Voso |
spellingShingle |
Emiliano Fabiani Laura Cicconi Anna Maria Nardozza Antonio Cristiano Marianna Rossi Tiziana Ottone Giulia Falconi Mariadomenica Divona Anna Maria Testi Ombretta Annibali Roberto Castelli Vladimir Lazarevic Eduardo Rego Pau Montesinos Jordi Esteve Adriano Venditti Matteo Della Porta William Arcese Francesco Lo‐Coco Maria Teresa Voso Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia Cancer Medicine AML ARID1A NGS ZBTB16‐RARA |
author_facet |
Emiliano Fabiani Laura Cicconi Anna Maria Nardozza Antonio Cristiano Marianna Rossi Tiziana Ottone Giulia Falconi Mariadomenica Divona Anna Maria Testi Ombretta Annibali Roberto Castelli Vladimir Lazarevic Eduardo Rego Pau Montesinos Jordi Esteve Adriano Venditti Matteo Della Porta William Arcese Francesco Lo‐Coco Maria Teresa Voso |
author_sort |
Emiliano Fabiani |
title |
Mutational profile of ZBTB16‐RARA‐positive acute myeloid leukemia |
title_short |
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_sort |
mutational profile of zbtb16‐rara‐positive acute myeloid leukemia |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2021-06-01 |
description |
Abstract 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. |
topic |
AML ARID1A NGS ZBTB16‐RARA |
url |
https://doi.org/10.1002/cam4.3904 |
work_keys_str_mv |
AT emilianofabiani mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT lauracicconi mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT annamarianardozza mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT antoniocristiano mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT mariannarossi mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT tizianaottone mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT giuliafalconi mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT mariadomenicadivona mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT annamariatesti mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT ombrettaannibali mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT robertocastelli mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT vladimirlazarevic mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT eduardorego mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT paumontesinos mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT jordiesteve mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT adrianovenditti mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT matteodellaporta mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT williamarcese mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT francescolococo mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia AT mariateresavoso mutationalprofileofzbtb16rarapositiveacutemyeloidleukemia |
_version_ |
1721374061619052544 |