Number and dynamics of micronuclei and near-tetraploidy predict prognosis in childhood acute leukaemia
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
37997902
DOI
10.5507/bp.2023.046
Knihovny.cz E-resources
- Keywords
- buccal micronuclei (Mn), children leukaemia, predictors,
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma * genetics MeSH
- Child MeSH
- Infant MeSH
- Humans MeSH
- Micronucleus Tests MeSH
- Micronuclei, Chromosome-Defective * MeSH
- Adolescent MeSH
- Polyploidy * MeSH
- Child, Preschool MeSH
- Prognosis MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: This study aims to identify factors possibly contributing to complications in children with acute leukaemia. Despite diverse etiological causes, similar processes trigger the process of cell malignancy. Genomic instability has received considerable attention in this context. METHOD: We conducted chromosomal analysis of bone marrow cells and measured the micronuclei (Mn) level in buccal cells over time. Statistical reliability assessment was performed using Analysis of variance (ANOVA), and the data were analyzed and visualized using the SPSS 12 statistical analysis software package. RESULTS: On the 15th day of treatment, our findings confirmed a statistically significant correlation (χ2=3.88, P=0.04) between the number of blasts in the bone marrow and unfavourable outcome in patients with a near-tetraploid chromosome clone. Additionally, on the 33rd day of treatment, we observed a correlation between an elevated number of Mn and relapses. DISCUSSION: While it is commonly believed that a hyperdiploid clone with >50 chromosomes in childhood acute lymphoblastic leukaemia confers favorable outcome, our study revealed partially heterogeneous results and poor prognosis in patients with a near-tetraploid clone. We have also identified a correlation between the Mn level on the 33rd day of treatment and the development of complications. It is possible that the increased Mn values and the occurrence of relapses were influenced by the individual patient's sensitivity to the genotoxic effect of the medication.
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Sehgelaia A. Childhood acute Leukemia. Tbilisi: Medical literature; 2018.
Teachey DT, Pui CH. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol 2019;20(3):e142-e154. doi: 10.1016/S1470-2045(19)30031-2 PubMed DOI
Phillips DH, Arlt VM. Genotoxicity: damage to DNA and its consequences. EXS 2009;99:87-110. doi: 10.1007/978-3-7643-8336-7_4 PubMed DOI
Zedginidze A, Namchevadze E, Jashiashvili S, Lomadze E. Develop a genetic prediction vectors for identification individual sensitivity of children with leukemia to genotoxicity of therapy. In: Mantskava MM, editor. International Multidisciplinary Conference on Biomedicine ABSTRACTS BOOK. Biomed 2020; 26-27 July, Shekvetili, Georgia. p. 56-57. doi: 10.6084/m9.figshare.12616655 DOI
Ormotsadze G, Shengelaia A, Chkhaidze I, Zedginidze A, Sanikidze T, Giorgobiani M, Sharashenidze G, Ormotsadze L. Space-time clustering of childhood leukemia in Tbilisi City. In: Nargiz Nachkebia, Nodar P. Mitagvaria, editors. Systemic, Cellular and Molecular Mechanisms of Physiological Functions and Their Disorders (Proceedings of I. Beritashvili Center for Experimental Biomedicine - 2021). Nova Science Publishers 2021; chapter 14.
Holland N, Bolognesi C, Krisch-Vlders M, Bonassi S, Zeiger E, Knnasmueller S, Fenech M. The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: The HUMN project perspective on current status and knowledge gaps. Mutat Res 2008;659(1-2):93-108. doi: 10.1016/j.mrrev.2008.03.007 PubMed DOI
Dávila-Rodríguez MI, Cortés-Gutiérrez EI, Hernández-Valdés R, Guzmán-Cortés K, De León-Cantú RE, Cerda-Flores RM, Báez-De la Fuente E. DNA damage in acute myeloid leukemia patients of Northern Mexico. Eur J Histochem 2017;61(4):2851. doi: 10.4081/ejh.2017.2851 PubMed DOI
Bakhoum SF, Cantley LC. The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment. Cell 2018;174(6):1347-1360. doi: 10.1016/j.cell.2018.08.027 PubMed DOI
Wang RC, Yang L, Tang Y, Bai O. Micronucleus Expression and Acute Leukemia Prognosis. Asian Pac J Cancer Prev 2013;14(9):5257-61. doi: 10.7314/apjcp.2013.14.9.5257 PubMed DOI
Hamurcu Z, Dönmez-Altuntas H, Patiroglu T. Basal level micronucleus frequency in stimulated lymphocytes of untreated patients with leukemia. Cancer Genet Cytogenet 2008;180(2):140-4. doi: 10.1016/j.cancergencyto.2007.10.009 PubMed DOI
Theda C, Hwang SH, Czajko A, Loke YJ, Leong P, Craig JM. Quantitation of the cellular content of saliva and buccal swab samples. Sci Rep 2018;8(1):6944. doi: 10.1038/s41598-018-25311-0 PubMed DOI
Paulsson K, Johansson B. High hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 200948(8):637-60. doi: 10.1002/gcc.20671 PubMed DOI
Attarbaschi A, Mann G, König M, Steiner M, Dworzak MN, Gadner H, Haas OA; Austrian Berlin-Frankfurt-Münster Cooperative Study Group. Near-tetraploidy in childhood B-cell precursor acute lymphoblastic leukemia is a highly specific feature of ETV6/RUNX1-positive leukemic cases. Genes Chromosomes Cancer 2006;45(6):608-11. doi: 10.1002/gcc.20324 PubMed DOI
Mkrtchyan H, Garcia Ney DR, DE Ventura ES, Liehr T, Felix GR, Marques-Salles T, Abdelhay E, Macedo Silva ML. Molecular cytogenetic studies characterize a near-triploid complex karyotype in a child with acute lymphoblastic leukemia. Cancer Genet Cytogenet 2010;197(1):71-4. doi: 10.1016/j.cancergencyto.2009.09.019 PubMed DOI
Dhillon VS, Deo P, Bonassi S, Fenech M. Lymphocyte micronuclei frequencies in skin, haematological, prostate, colorectal and esophageal cancer cases: A systematic review and meta-analysis. Mutation Research/Reviews in Mutation Research 2021;787:108372. doi:10.1016/j.mrrev.2021.108372 PubMed DOI
Sagari SG, Babannavar R, Lohra A, Kodgi A, Bapure S, Rao Y, J A, Malghan M. Micronuclei frequencies and nuclear abnormalities in oral exfoliated cells of nuclear power plant workers. J Clin Diagn Res 2014;8(12):ZC15-7. doi: 10.7860/JCDR/2014/9059.5240 PubMed DOI