Serum-profiling identifies ibrutinib as a treatment option for young adults with B-cell acute lymphoblastic leukaemia

Jordaens, Stephanie; Cooksey, Leah; Bonney, Stephanie; Orchard, Laurence; Coutinho, Matthew; Van Tendeloo, Viggo; Mills, Ken I.; Orchard, Kim; Guinn, Barbara

Abstract

Acute lymphoblastic leukaemia (ALL) is a haematological malignancy that is characterized by the uncontrolled proliferation of immature lymphocytes. 80 % of cases occur in children where ALL is well understood and treated. However it has a devastating affects on adults, where multi-agent chemotherapy is the standard of care with allogeneic stem cell transplantation for those who are eligible. New treatments are required to extend remission and prevent relapse to improve patient survival rates.
We used serum profiling to compare samples from presentation adult B-ALL patients with age- and sex-matched healthy volunteer (HV) sera and identified 69 differentially recognised antigens (p≤0.02). BMX, DCTPP1 and VGLL4 showed no differences in transcription between patients and healthy donors but were each found to be present at higher levels in B-ALL patient samples than HVs by ICC. BMX plays a crucial role in the Bruton’s Tyrosine Kinase (BTK) pathway which is bound by the BTK inhibitor, ibrutinib, suggesting adult B-ALL would also be a worthy target patient group for future clinical trials.
We have shown the utility of proto-array analysis of B-ALL patient sera, predominantly from young adults, to help characterise the B-ALL immunome and identified a new target patient population for existing small molecule therapy.

Citation

Jordaens, S., Cooksey, L., Bonney, S., Orchard, L., Coutinho, M., Van Tendeloo, V., Mills, K. I., Orchard, K., & Guinn, B. (2020). Serum-profiling identifies ibrutinib as a treatment option for young adults with B-cell acute lymphoblastic leukaemia. British journal of haematology, 189(3), 500-512. https://doi.org/10.1111/bjh.16407

• Journal Article Type: Article
• Acceptance Date: Nov 10, 2019
• Online Publication Date: Feb 16, 2020
• Publication Date: 2020-05
• Deposit Date: Jan 28, 2020
• Publicly Available Date: Feb 17, 2021
• Journal: British Journal of Haematology
• Print ISSN: 0007-1048
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 189
• Issue: 3
• Pages: 500-512
• DOI: https://doi.org/10.1111/bjh.16407
• Keywords: acute lymphoblastic leukaemia; antigen identification; serum profiling; immunotherapy; survivin; bone marrow tyrosine kinase on chromosome X (BMX); acute lymphoblastic leukaemia; Ibrutinib; antigen identification; BMX; protein arrays
• Public URL: https://hull-repository.worktribe.com/output/3129304
• Contract Date: Jan 28, 2020