B-lineage antigens that are useful to substitute CD19 for minimal residual disease monitoring in B cell precursor acute lymphoblastic leukemia after CD19 targeting

Background: The potential loss of CD19 during targeted treatment of B cell precursor acute lymphoblastic leukemia (BCP-ALL) can hamper flow cytometric minimal residual disease (MRD) monitoring. In the current study, we present expression data for antigens that are candidates for CD19 substitution: surface CD22, CD24, CD10, and intracellular (i) CD79a.

Methods: Bone marrow samples from 519 consecutive children (below 18 y.o.) with primary BCP-ALL were studied with a focus on expression of CD19, CD10, CD22, CD24, and iCD79a. As these antigens are planned to be used as substitutions for CD19 for primary B cell gating, only total expression on the leukemic population (≥95% cells) was considered appropriate.

Results: It was found that each of these antigens is totally expressed in nearly 90% of patients. For each single marker, a subgroup of patients without complete positivity presented with BCP-ALL harboring diverse cytogenetic and molecular genetic aberrations. Based on expression data, we have developed algorithm of simultaneous application of these antigens for initial B-lineage compartment gating, that is applicable for nearly all patients after CD19 targeting.

Conclusion: We conclude that the addition of CD22, CD24, and iCD79a to the conventional antibody panel and their application together with CD10 allow for the identification of B-lineage compartment including residual tumor blasts, for MFC-MRD searching in virtually all patients with BCP-ALL after CD19-directed treatment.