Adult B-Cell Acute Lymphoblastic Leukaemia Antigens and Enriched Pathways Identify New Targets for Therapy
Mohamed, Eithar; Goodman, Sara; Cooksey, Leah; Fletcher, Daniel M; Dean, Olivia; Boncheva, Viktoriya B; Mills, Ken I; Orchard, Kim H; Guinn, Barbara-Ann
Authors
Eithar Mohamed
Sara Goodman
Leah Cooksey
Daniel M Fletcher
Olivia Dean
Viktoriya B Boncheva
Ken I Mills
Kim H Orchard
Dr Barbara Guinn B.Guinn@hull.ac.uk
Reader in Biomedical Sciences
Abstract
Background: Adult B-cell acute lymphoblastic leukaemia (aB-ALL) is charac-terised by abnormal differentiation and proliferation of lymphoid progenitors. Despite a significant improvement in relapse-free and overall survival for children with BALL , aB-ALL has a particularly poor prognosis with a 5-year survival rate of 20%. First remission is achieved for most patients, but relapse is common with a high associated mortality. New treatments such as immunotherapy offer an opportunity to extend remission and prevent relapse. Methods: aB-ALL antigens were identified using different sources-immunoscreening, protoarrays, two microarrays and one cancer-testis antigen database, and a review of the genomic analyses of aB-ALL. A total of 385 aB-ALL-associated gene products were examined for their association with patient survival. Results: We identified 87 transcripts with differential expression between aB-ALL and healthy volunteers (peripheral blood, bone marrow and purified CD19 + cells), and 42 that were associated with survival. Enrichr analysis showed that the Transforming Growth Factor-β (TGFβ), Wnt and Hippo pathways were highly represented (p < 0.02). We found that SOX4 and ROCK1 were upregulated in all types of BALL (ROCK1 having a p < 0.001 except in t(8;14) patients), as well as SMAD3 and TEAD4 upregulation being associated with survival (p = 0.0008, 0.05 and 0.001, respectively). Expression of each aB-ALL antigen was verified by qPCR, but only TEAD4 showed significant transcript upregulation in aB-ALL compared to healthy volunteer CD19+ cells (p = 0.01). Conclusions: We have identified a number of antigens and their pathways that play key roles in aB-ALL and may act as useful targets for future immunotherapy strategies.
Citation
Mohamed, E., Goodman, S., Cooksey, L., Fletcher, D. M., Dean, O., Boncheva, V. B., Mills, K. I., Orchard, K. H., & Guinn, B.-A. (2025). Adult B-Cell Acute Lymphoblastic Leukaemia Antigens and Enriched Pathways Identify New Targets for Therapy. Onco, 5(2), Article 19. https://doi.org/10.3390/onco5020019
