Immaturity Associated Antigens Are Lost During Induction for T Cell Lymphoblastic Leukemia: Implications for Minimal Residual Disease Detection

摘要

Background: Induction chemotherapy for acute leukemia often leads to antigenic shifts in residual abnormal blast populations. Studies in precursor B cell ALL (B-ALL) have demonstrated that chemotherapy commonly results in the loss of antigens associated with immaturity, limiting their utility for minimal residual disease (MRD) detection. Little information is available about the stability of these antigens in precursor T cell ALL (T-ALL) though it is presumed that CD99 and terminal deoxynucleotidyl transferase (TdT) are highly informative based on limited studies. Methods: In a longitudinal investigation, we explored patterns of lineage specific and immaturity-associated antigens in T-ALL in a large cohort of patients treated under the multicenter Children's Oncology Group (COG) protocol. All samples were analyzed using multicolor flow cytometry in a standardized fashion at a single institution. Results: We report that markers of immaturity particularly, TdT and CD99, dramatically decline on leukemic blasts during therapy. CD34 and CD10 expression is confined to a minority of pretreatment samples and is also not stable. In contrast, lineage-associated markers including CD2, CD3, CD4, CD5, CD7, and CD8 failed to show significant trends. Conclusions: Our study strongly argues for expansion of immunophenotyping panels for T-ALL MRD to decrease reliance on immature antigens. This study represents the first demonstration of consistent immunophenotypic shifts in T-ALL.