New targets for therapy: antigen identification in adults with B-cell acute lymphoblastic leukaemia

Abstract

Acute lymphoblastic leukaemia (ALL) in adults is a rare and difficult-to-treat cancer that is characterised by excess lymphoblasts in the bone marrow. Although many patients achieve remission with chemotherapy, relapse rates are high and the associated impact on survival devastating. Most patients receive chemotherapy and for those whose overall fitness supports it, the most effective treatment to date is allogeneic stem cell transplant that can improve overall survival rates in part due to a 'graft-versus-leukaemia' effect. However, due to the rarity of this disease, and the availability of mature B-cell antigens on the cell surface, few new cancer antigens have been identified in adult BALL that could act as targets to remove residual disease in first remission or provide alternative targets for escape variants if and when current immunotherapy strategies fail. We have used RT-PCR analysis, literature searches, antibody-specific profiling and gene expression microarray analysis to identify and prioritise antigens as novel targets for the treatment of adult BALL .

Promising genes and variants to reduce chemotherapy adverse effects in acute lymphoblastic leukemia

“…BTK has been found abnormally expressed in ALL [ 148 , 149 ] and pre-B cells have shown high sensitivity to ibrutinib in preclinical models of B-ALL [148] . Other example is survivin, an apoptosis inhibitor and cell cycle regulator that is expressed in many types of tumors (including ALL) and is associated with chemoresistance [ 150 , 151 ]. Several clinical trials have found survivin as a therapeutic target to ALL [152] , [153] , [154] .…”

Isolated Myeloperoxidase Immunohistochemical Expression in Bone Marrow Biopsy Depicts Clinical Outcomes in Adults with Typical B-Acute Lymphoblastic Leukemia

“…Despite the significant improvement in pediatric patients' outcomes, B-ALL represents a devastating, poor-prognosis disease in adults as only 30-40% of those patients achieve long-term remission (Terwilliger and Abdul-Hay, 2017;Jordaens et al, 2020). In the era of personalized medicine, it may be important to identify explicit prognostic parameters that allow better patients' stratification aiming to provide the optimum therapeutic regimen for each particular case.…”