Among patients with B-lineage acute lymphoblastic leukemia (ALL), the VpreB1 subunit of the immunoglobulin heavy chain surrogate light chain (SLC) may represent a novel therapeutic target, according to research published in Blood Advances.
The pre-B cell receptor (BCR), which is involved in immature B cell selection and expansion, consists of 5 units, of which 1 is the SLC. Impaired pre-BCR activity may, furthermore, lead to the development and proliferation of B cell cancers, including ALL.
While existing targeted therapies have improved outcomes among patients with ALL, relapse is common, representing a need for novel therapies for this patient population. Previous research has suggested that incubating patient blasts with monoclonal antibodies targeting VpreB—CD179a—may induce apoptosis.
For this study, researchers evaluated whether CD179a may be highly expressed on B lymphoblasts, and consequently represent a promising therapeutic target among patients with B-lineage ALL.
Overall, 36 patient samples from individuals accrued to a Children’s Oncology Group study were evaluated using a minimal residual disease (MRD) flow panel to evaluate pre-BCR expression. CD179a expression was also evaluated in 16 samples at end-induction; these samples had at least 1% MRD.
The majority (32) of cases were at the pre-B stage of developmental arrest, while 4 cases were at the pro-B stage. Analysis suggested that CD179a was present in at least 20% of B lymphoblasts. At end-induction, CD179a was expressed in all B lymphoblasts.
CD179a was, according to the authors, expressed in B-lineage ALL regardless of genotype or disease risk status. The authors proposed to “assess in future clinical trials whether immunotherapies against the pre-BCR might spare a patient’s mature B-cell repertoire.”
Winter SS, McCaustland A, Qu C, et al. VpreB surrogate light chain expression in B-lineage ALL: a report from the Children’s Oncology Group. Blood Adv. 2022;6(2):585-589. doi:10.1182/bloodadvances.2021005245