Cytogenetics and associated mutation profile in patients with acute monocytic leukemia
| Autor: | Yiwu Sun, Shan-Shan Xing, Tong Wang, Mengjie Li, Yimin Shen, Biao Wang, Hongying Chao, Yu Gao |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.medical_specialty NPM1 Adolescent Clinical Biochemistry 030204 cardiovascular system & hematology Gene mutation medicine.disease_cause 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Humans Acute monocytic leukemia Mutation frequency Child In Situ Hybridization Fluorescence Aged Gene Rearrangement biology medicine.diagnostic_test business.industry Reverse Transcriptase Polymerase Chain Reaction Biochemistry (medical) Cytogenetics High-Throughput Nucleotide Sequencing Hematology General Medicine Middle Aged medicine.disease Neoplasm Proteins KMT2A Karyotyping Leukemia Monocytic Acute biology.protein Cancer research Female KRAS business Nucleophosmin 030215 immunology Fluorescence in situ hybridization |
| Zdroj: | International journal of laboratory hematology. 41(4) |
| ISSN: | 1751-553X |
| Popis: | INTRODUCTION Cytogenetics and molecular testings for disease classifying and prognosis estimation are becoming routine in clinical practice. However, the molecular characteristics of acute monocytic leukemia (AML-M5) remain unclear. The aim of this study was to investigate the association between karyotypes and gene mutations, especially in AML-M5 patients with 11q23/KMT2A (MLL) rearrangement and normal karyotype. METHODS A total of 126 de novo AML-M5 patients were screened for mutations in the 51 genes known or suspected to have a role in myeloid malignancies or in monocytic differentiation using next-generation sequencing (NGS). Chromosome karyotype analysis was performed by R-banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT-PCR). RESULTS Of the 126 patients, one or more mutations were detected in 83.3% patients. FLT3-ITD and NRAS had the highest mutation frequency, followed by NPM1, DNMT3A, TET2, KRAS, and RUNX1. We also identified a significant difference in mutational spectrums between KMT2A-rearranged (KMT2Ar) patients and normal karyotype (NK) patients, as reflected in the average number of gene mutations per patient (1.66 vs 2.46), and in the frequencies of commonly mutated genes (FLT3-ITD: 6% vs 43.5%; NPM1: 0% vs 43.5%; RUNX1: 2.0% vs 15.2%; DNMT3A: 4% vs 26.1%; KRAS: 24.0% vs 4.35%). Patients harboring ≥3 mutations showed much lower complete remission rate than that with double mutations (P = 0.043) in high-risk group. CONCLUSION There was a significantly different mutation profile between KMT2Ar-patients and NK patients. Our research provided new insight into the molecular characteristics of AML-M5. |
| Databáze: | OpenAIRE |
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