VpreB Surrogate Light Chain Expression in B-Lineage ALL: A Report from the Children's Oncology Group

Immunotherapies directed against B-cell surface markers have been a common developmental strategy to treat B-cell malignancies. The IgH surrogate light chain (SLC), comprised of the VpreB1 (CD179a) and Lamda5 (CD179b) subunits is expressed on pro- and pre-B cells where it governs preBCR-mediated autonomous survival signaling. We hypothesized that the pre-BCR might merit the development of targeted immunotherapies to decouple "autonomous" signaling in B-lineage acute lymphoblastic leukemia (B-ALL). We used the COG minimal residual disease (MRD) flow panel to assess pre-BCR expression in 36 primary patient samples accrued to COG standard and high-risk B-ALL studies through AALL03B1. We also assessed CD179a expression in 16 cases with Day 29 end-induction samples, pre-selected to have ≥1% MRD. All analyses were performed on a 6-color Becton-Dickinson flow cytometer in a CLIA/CAP-certified laboratory. Among 36 cases tested, thirty-two were at the pre-B and four were at the pro-B stages of developmental arrest. One or both mAbs showed that CD179a was present in ≥20% of the B-lymphoblast population. All cases expressed CD179a in the end-induction B-lymphoblast population. The CD179a component of the SLC is commonly expressed in B-ALL, regardless of genotype, stage of developmental arrest or NCI risk-status.