VpreB surrogate light chain expression in B-lineage ALL: A report from the Children's Oncology Group

Academic Article

Abstract

  • Immunotherapies directed against B-cell surface markers have been a common developmental strategy to treat B-cell malignancies. The immunoglobulin heavy chain surrogate light chain (SLC), comprising the VpreB1 (CD179a) and Lamda5 (CD179b) subunits, is expressed on pro- and pre-B cells, where it governs pre-B-cell receptor (BCR)- 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 Children's Oncology Group (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, preselected to have$1%MRD. All analyses were performed on a 6-color Becton- Dickinson flow cytometer in a Clinical Laboratory Improvement Amendment/College of American Pathologist-certified laboratory. Among 36 cases tested, 32 cases were at the pre-B and 4 cases were at the pro-B stages of developmental arrest. One or both monoclonal antibodies (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 National Cancer Institute risk status.
  • Published In

  • Blood Advances  Journal
  • Digital Object Identifier (doi)

    Author List

  • Winter SS; McCaustland A; Qu C; Simeona N; Heerema NA; Carroll AJ; Wood BL; Gheorghe G; Mullighan CG; Wilson BS
  • Start Page

  • 585
  • End Page

  • 589
  • Volume

  • 6
  • Issue

  • 2