Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia
| Autor: | Anh Nhi Tran, Vasilios Zachariadis, Mats Heyman, Jessica Nordlund, Daniel Nilsson, Magnus Nordenskjöld, Arja Harila-Saari, Fulya Taylan, Ingegerd Ivanov Öfverholm, Leonie Saft, Gudmar Lönnerholm, Yanara Marincevic-Zuniga, Gisela Barbany, Ann Nordgren, Ann-Christine Syvänen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Poor prognosis Lymphoblastic Leukemia transcriptome sequencing Biology Article Chromatin remodeling Cytogenetics 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Gene expression Humans Hematologi Child Gene Chromosome Aberrations mp-wgs iAMP21 Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Protein-Tyrosine Kinases Chromatin Assembly and Disassembly Transcriptome Sequencing Chromatin Assembly Factor-1 Oncology 030220 oncology & carcinogenesis Acute lymphoblastic leukemia gene expression analysis Cancer research Chromosome 21 Tyrosine kinase 030215 immunology |
| Zdroj: | Leuk Lymphoma |
| Popis: | Intrachromosomal amplification of chromosome 21 (iAMP21) is a cytogenetic subtype associated with relapse and poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). The biology behind the high relapse risk is unknown and the aim of this study was to further characterize the genomic and transcriptional landscape of iAMP21. Using DNA arrays and sequencing, we could identify rearrangements and aberrations characteristic for iAMP21. RNA sequencing revealed that only half of the genes in the minimal region of amplification (20/45) were differentially expressed in iAMP21. Among them were the top overexpressed genes (p < 0.001) in iAMP21 vs. BCP ALL without iAMP21 and three candidate genes could be identified, the tyrosine kinase gene DYRK1A and chromatin remodeling genes CHAF1B and SON. While overexpression of DYRK1A and CHAF1B is associated with poor prognosis in malignant diseases including myeloid leukemia, this is the first study to show significant correlation with iAMP21-positive ALL. |
| Databáze: | OpenAIRE |
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