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ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype
Acute myeloid leukemia with myelodysplasia‐related changes (AML‐MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency of ASXL1 mutations have been described in this leukemia...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286456/ https://www.ncbi.nlm.nih.gov/pubmed/32216059 http://dx.doi.org/10.1002/cam4.2947 |
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author | Prats‐Martín, Concepción Burillo‐Sanz, Sergio Morales‐Camacho, Rosario M. Pérez‐López, Olga Suito, Milagros Vargas, Maria T. Caballero‐Velázquez, Teresa Carrillo‐Cruz, Estrella González, José Bernal, Ricardo Pérez‐Simón, José A. |
author_facet | Prats‐Martín, Concepción Burillo‐Sanz, Sergio Morales‐Camacho, Rosario M. Pérez‐López, Olga Suito, Milagros Vargas, Maria T. Caballero‐Velázquez, Teresa Carrillo‐Cruz, Estrella González, José Bernal, Ricardo Pérez‐Simón, José A. |
author_sort | Prats‐Martín, Concepción |
collection | PubMed |
description | Acute myeloid leukemia with myelodysplasia‐related changes (AML‐MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency of ASXL1 mutations have been described in this leukemia. We sequenced ASXL1 gene mutations in 61 patients with AML‐MRC and 46 controls with acute myeloid leukemia without other specifications (AML‐NOS) to identify clinical, cytomorphologic, and cytogenetic characteristics associated with ASXL1 mutational status. Mutated ASXL1 (ASXL1+) was observed in 31% of patients with AML‐MRC compared to 4.3% in AML‐NOS. Its presence in AML‐MRC was associated with older age, a previous history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN), leukocytosis, presence of micromegakaryocytes in bone marrow, lower number of blasts in bone marrow, myelomonocytic/monocytic morphological features and normal karyotype. ASXL1 mutation was not observed in patients with myelodysplastic syndrome‐related cytogenetic abnormalities or TP53 mutations. Differences in terms of overall survival were found only in AML‐MRC patients without prior MDS or MDS/MPN and with intermediate‐risk karyotype, having ASXL1+ patients a worst outcome than ASXL1−. We conclude that the ASXL1 mutation frequency is high in AML‐MRC patients being its presence associated with specific characteristics including morphological signs of dysplasia. This association raises the possible role of ASXL1 as a surrogate marker in AML‐MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML‐MRC with intermediate‐risk karyotype. |
format | Online Article Text |
id | pubmed-7286456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72864562020-06-11 ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype Prats‐Martín, Concepción Burillo‐Sanz, Sergio Morales‐Camacho, Rosario M. Pérez‐López, Olga Suito, Milagros Vargas, Maria T. Caballero‐Velázquez, Teresa Carrillo‐Cruz, Estrella González, José Bernal, Ricardo Pérez‐Simón, José A. Cancer Med Clinical Cancer Research Acute myeloid leukemia with myelodysplasia‐related changes (AML‐MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency of ASXL1 mutations have been described in this leukemia. We sequenced ASXL1 gene mutations in 61 patients with AML‐MRC and 46 controls with acute myeloid leukemia without other specifications (AML‐NOS) to identify clinical, cytomorphologic, and cytogenetic characteristics associated with ASXL1 mutational status. Mutated ASXL1 (ASXL1+) was observed in 31% of patients with AML‐MRC compared to 4.3% in AML‐NOS. Its presence in AML‐MRC was associated with older age, a previous history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN), leukocytosis, presence of micromegakaryocytes in bone marrow, lower number of blasts in bone marrow, myelomonocytic/monocytic morphological features and normal karyotype. ASXL1 mutation was not observed in patients with myelodysplastic syndrome‐related cytogenetic abnormalities or TP53 mutations. Differences in terms of overall survival were found only in AML‐MRC patients without prior MDS or MDS/MPN and with intermediate‐risk karyotype, having ASXL1+ patients a worst outcome than ASXL1−. We conclude that the ASXL1 mutation frequency is high in AML‐MRC patients being its presence associated with specific characteristics including morphological signs of dysplasia. This association raises the possible role of ASXL1 as a surrogate marker in AML‐MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML‐MRC with intermediate‐risk karyotype. John Wiley and Sons Inc. 2020-03-26 /pmc/articles/PMC7286456/ /pubmed/32216059 http://dx.doi.org/10.1002/cam4.2947 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://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 Prats‐Martín, Concepción Burillo‐Sanz, Sergio Morales‐Camacho, Rosario M. Pérez‐López, Olga Suito, Milagros Vargas, Maria T. Caballero‐Velázquez, Teresa Carrillo‐Cruz, Estrella González, José Bernal, Ricardo Pérez‐Simón, José A. ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype |
title |
ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype |
title_full |
ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype |
title_fullStr |
ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype |
title_full_unstemmed |
ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype |
title_short |
ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype |
title_sort | asxl1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia‐related changes and normal karyotype |
topic | Clinical Cancer Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286456/ https://www.ncbi.nlm.nih.gov/pubmed/32216059 http://dx.doi.org/10.1002/cam4.2947 |
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