Transcriptomic Profiling of Pediatric Acute Lymphoblastic Leukemia Subtypes Identifies Novel Prognostic Markers

Haneen  Abdulrahman Shaban; Waleed Nazal  Hosi; Semaa  Abdulrahman Shaban; Ahmed  AbdulJabbar Suleiman

doi:10.18502/ijpho.v16i1.20422

Haneen Abdulrahman Shaban Salahadeen general hospital, ministry of Health, Tikrit, Iraq
Waleed Nazal Hosi College of Science, University of Tikrit, Tikrit, Iraq
Semaa Abdulrahman Shaban College of Science, University of Tikrit, Tikrit, Iraq
Ahmed AbdulJabbar Suleiman Department of Biotechnology, College of Science, University of Anbar, Ramadi, Anbar, Iraq

DOI: https://doi.org/10.18502/ijpho.v16i1.20422

Keywords: Acute Lymphoblastic Leukemia, Chromosomal Abnormalities, Differential Expression Analysis, HOXA, Pediatric, Subtyping

Abstract

Background: Pediatric acute lymphoblastic leukemia (ALL) encompasses more than 20 molecular subtypes with diverse genetic and prognostic profiles. The 11q subtype, characterized by KMT2A rearrangements, exhibits an aggressive clinical course compared with favorable subtypes such as high hyperdiploidy (HeH) and dic (9; 20). This study aimed to elucidate the distinct transcriptomic signature of the 11q-rearranged pediatric ALL subtype relative to HeH and dic (9; 20) to identify novel prognostic markers.

Materials and Methods: Comparative observational study was done by gene expression profiles of 11q ALL (n = 5) were compared with dic (9; 20) ALL (n = 6) and HeH ALL (n = 18) using the GEO2R tool on the GSE47051 microarray dataset. Differentially expressed genes (DEGs) were defined as those with p < 0.05 and |log₂ fold change| > 1.0. Common DEGs across both comparisons were identified using Venny 2.1.0, and their protein–protein interaction networks and functional enrichment were analyzed using STRING.

Results: A total of 241 common DEGs were identified in 11q ALL, including 151 upregulated and 90 downregulated genes (p < 0.05). Prominent upregulated genes included members of the HOXA cluster (HOXA3, HOXA4, HOXA5, HOXA7, HOXA10) and MEIS1 (p = 0.001), reflecting activation of leukemogenic transcriptional programs. Conversely, genes involved in B-cell differentiation, such as BLNK and MS4A1/CD20, were significantly downregulated (p = 0.004). Enrichment analysis revealed that upregulated genes were significantly associated with focal adhesion, protein kinase binding, and cell migration pathways (p < 0.01), while downregulated genes were linked to B-cell activation, DNA repair, and chromosomal stability (p < 0.05).

Conclusion: The 11q-rearranged ALL subtype demonstrates a distinct transcriptional landscape characterized by HOXA–MEIS1 axis activation and suppression of normal B-cell signaling. These transcriptomic alterations likely underpin its aggressive phenotype and could inform risk stratification and targeted therapeutic development for high-risk pediatric ALL patients.