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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)500-512
Number of pages13
JournalBritish Journal of Haematology
Volume189
Issue number3
Early online date16 Feb 2020
DOIs
Publication statusPublished - 29 Apr 2020

Bibliographical note

© 2020 British Society for Haematology and John Wiley & Sons Ltd.

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