Application of Gene Expression Microarray for the Classification of Ph-Like B-Cell Acute Lymphoblastic Leukemia.

Autor: Thangrua N; Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand., Siriboonpiputtana T; Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Rerkamnuaychoke B; Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Chareonsirisuthigul T; Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Korkiatsakul V; Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Pongphitcha P; Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Mukda E; Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, Thailand., Chutipongtanate S; Department of Environmental and Public Health Sciences, University of Cincinnati, Ohio, USA., Pakakasama S; Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Jazyk: angličtina
Zdroj: International journal of laboratory hematology [Int J Lab Hematol] 2024 Oct 02. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1111/ijlh.14370
Abstrakt: Introduction: Ph-like ALL has gene expression profile similar to Ph-positive ALL but without the BCR::ABL1 fusion. The disease presents higher rates of severe clinical features and is associated with unfavorable outcomes. There is still no standard pipeline for molecular characterization of the disease, and no valid predictor gene panel is available worldwide.
Methods: We performed expression microarray on 25 B-cell ALL and 6 Ph-positive B-cell ALL to cluster and identify the transcriptional signature of Ph-like ALL. qRT-PCR was used to confirm the expression of candidate genes.
Results: Four out of 25 samples (16%) shared gene expression signatures related to and clustered with control Ph-positive samples. Analysis of genes differentially expressed in Ph-like B-cell ALL and evidentially functional in normal blood cell development and leukemogenesis, we selected genes as potential biomarkers for Ph-like B-cell ALL in our dataset: ADGRE2, CD9, EPHA7, FAM129C, TCL1A, and VPREB1. Those genes were filtered by Ph-like gene signatures obtained from distinct reliable data, resulting in five genes, CA6, CHN2, JAK1, JCHAIN, and PON2, selected for validation by qRT-PCR. The Ct values of genes, including CA6 (p = 0.0017), PON2 (p = 0.0210), TCL1A (p = 0.0064), and VPREB1 (p = 0.0338), were significant in Ph-like ALL. GSEA analysis identified VPREB1 as enrichment in the KRAS signaling pathway, and several genes that interact with VPREB1 were reported as critical molecules involved in the leukemogenesis of B-cell ALL.
Conclusion: In summary, we demonstrate using a gene expression microarray for classifying Ph-like B-cell ALL and highlight VPREB1 as a potential biomarker for this disease.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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