Mutational profile of ZBTB16-RARA-positive acute myeloid leukemia
(2021) In Cancer Medicine 10(12). p.3839-3847- 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... (More)
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.
(Less)
- author
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- AML, ARID1A, NGS, ZBTB16-RARA
- in
- Cancer Medicine
- volume
- 10
- issue
- 12
- pages
- 3839 - 3847
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85106623351
- pmid:34042280
- ISSN
- 2045-7634
- DOI
- 10.1002/cam4.3904
- language
- English
- LU publication?
- no
- additional info
- Funding Information: This work was supported by AIRC 5×1000 call "Metastatic disease: the key unmet need in oncology" to MYNERVA project, #21267 (MYeloid Neoplasms Research Venture AIRC. A detailed description of the MYNERVA project is available at http://www.progettoagimm.it ), PRIN grant no. 2017WXR7ZT to MTV, and the Innovative Medicines Initiative (IMI) 2 project “HARMONY”, no. 116026 to MTV. Publisher Copyright: © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
- id
- 75a39a19-18a0-4e1a-89db-ba6308b54c51
- date added to LUP
- 2021-06-06 08:12:19
- date last changed
- 2024-06-15 12:08:02
@article{75a39a19-18a0-4e1a-89db-ba6308b54c51,
abstract = {{<p>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.</p>}},
author = {{Fabiani, Emiliano and Cicconi, Laura and Nardozza, Anna Maria and Cristiano, Antonio and Rossi, Marianna and Ottone, Tiziana and Falconi, Giulia and Divona, Mariadomenica and Testi, Anna Maria and Annibali, Ombretta and Castelli, Roberto and Lazarevic, Vladimir and Rego, Eduardo and Montesinos, Pau and Esteve, Jordi and Venditti, Adriano and Della Porta, Matteo and Arcese, William and Lo-Coco, Francesco and Voso, Maria Teresa}},
issn = {{2045-7634}},
keywords = {{AML; ARID1A; NGS; ZBTB16-RARA}},
language = {{eng}},
number = {{12}},
pages = {{3839--3847}},
publisher = {{Wiley-Blackwell}},
series = {{Cancer Medicine}},
title = {{Mutational profile of ZBTB16-RARA-positive acute myeloid leukemia}},
url = {{http://dx.doi.org/10.1002/cam4.3904}},
doi = {{10.1002/cam4.3904}},
volume = {{10}},
year = {{2021}},
}