Analysis of SNP Array Abnormalities in Patients with DE NOVO Acute Myeloid Leukemia with Normal Karyotype.
Adult
Aged
Aged, 80 and over
Chromosome Aberrations
DNA Copy Number Variations
Female
Follow-Up Studies
High-Throughput Nucleotide Sequencing
Humans
Karyotype
Leukemia, Myeloid, Acute
/ genetics
Loss of Heterozygosity
Male
Middle Aged
Nucleophosmin
Polymorphism, Single Nucleotide
Prognosis
Prospective Studies
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 04 2020
03 04 2020
Historique:
received:
11
09
2018
accepted:
28
02
2020
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Nearly 50% of patients with de novo acute myeloid leukemia (AML) harbor an apparently normal karyotype (NK) by conventional cytogenetic techniques showing a very heterogeneous prognosis. This could be related to the presence of cryptic cytogenetic abnormalities (CCA) not detectable by conventional methods. The study of copy number alterations (CNA) and loss of heterozygozity (LOH) in hematological malignancies is possible using a high resolution SNP-array. Recently, in clinical practice the karyotype study has been complemented with the identification of point mutations in an increasing number of genes. We analyzed 252 de novo NK-AML patients from Hospital La Fe (n = 44) and from previously reported cohorts (n = 208) to identify CCA by SNP-array, and to integrate the analysis of CCA with molecular alterations detected by Next-Generation-sequencing. CCA were detected in 58% of patients. In addition, 49% of them harbored CNA or LOH and point mutations, simultaneously. Patients were grouped in 3 sets by their abnormalities: patients carrying several CCA simultaneously, patients with mutations in FLT3, NPM1 and/or DNMT3A and patients with an amalgam of mutations. We found a negative correlation between the number of CCA and the outcome of the patients. This study outlines that CCA are present in up to 50% of NK-AML patients and have a negative impact on the outcome. CCA may contribute to the heterogeneous prognosis.
Identifiants
pubmed: 32246042
doi: 10.1038/s41598-020-61589-9
pii: 10.1038/s41598-020-61589-9
pmc: PMC7125150
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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