Altered Transcriptome in Pediatric AML Compared with Normal Hematopoiesis

Fan Y, Hu Y, Yan C, Chen Q, Nguyen C, Dunn BK, Ries RE, Bolouri H, Smith JL, Kolb EA, Meshinchi S, Meerzaman D.

British Journal of Cancer Research

January 01, 2020

Gene expression profiling has been used to identify specific genes and pathways found within the different subsets of acute myeloid leukemia (AML). Prior studies have sought to characterize genetic differences within the subgroups themselves but no study to date has examined how gene expression patterns found in AML differ from normal hematopoiesis. In this study, we compared diagnostic bone marrow specimens obtained from 473 AML pediatric patients with normal bone marrow (NBM) from healthy individuals (N=20). An initial comparison of AML vs. NBM transcriptomes identified 2,625 differentially expressed genes (DEGs), with DUSP10 and MYBL1 as the most upregulated and downregulated genes. Comparing NBM with each AML cytogenetic subgroup resulted in 2,000-3,000 DEGs, with t(8;21) vs. NBM having the largest number of 3,367 DEGs. Three Cancer Testis Antigens (CTAs), MSLN, PRAME and CCNA1 were identified by all comparisons. Among them, CCNA1 was most significantly upregulated in AML vs. NBM. MSLN was highly expressed in most inv(16) samples whereas PRAME was highly expressed in the majority of t(8;21) samples. GSEA (Gene Set Enrichment Analysis) for DEGs showed tumorigenesis and immune related terms: inv(16) was linked to natural killer cell mediated cytotoxicity; t(8;21) and normal karyotype were related to T cell receptor signaling; MLL-rearrangement subtype was associated with PI3K-Akt signaling pathway. Distinctive linkage for increased or decreased interleukin levels were also indicated for each subtype. Together our findings suggest several genes and gene pathways within the AML subgroups that may serve as future biomarkers for disease or as targets for new immunotherapies.

Last updated: July 22, 2021