Immunophenotypic shift in the B‐cell precursors from regenerating bone marrow samples: A critical consideration for measurable residual disease assessment in B‐lymphoblastic leukemia

Accurate knowledge of expression patterns/levels of commonly used MRD markers in regenerative normal‐B‐cell‐precursors (BCP) is highly desirable to distinguish leukemic‐blasts from regenerative‐BCP for multicolor flow cytometry (MFC)‐based measurable residual disease (MRD) assessment in B‐lymphoblastic leukemia (B‐ALL). However, the data highlighting therapy‐related immunophenotypic‐shift in regenerative‐BCPs is scarce and limited to small cohort. Herein, we report the in‐depth evaluation of immunophenotypic shift in regenerative‐BCPs from a large cohort of BALL‐MRD samples. Ten‐color MFC‐MRD analysis was performed in pediatric‐BALL at the end‐of‐induction (EOI), end‐of‐consolidation (EOC), and subsequent‐follow‐up (SFU) time‐points. We studied normalized‐mean fluorescent intensity (nMFI) and coefficient‐of‐variation of immunofluorescence (CVIF) of CD10, CD19, CD20, CD34, CD38, and CD45 expression in regenerative‐BCP (early, BCP1 and late, BCP2) from 200 BALL‐MRD samples, and compared them with BCP from 15 regenerating control (RC) TALL‐MRD samples and 20 treatment‐naïve bone‐marrow control (TNSC) samples. Regenerative‐BCP1 showed downregulation in CD10 and CD34 expression with increased CVIF and reduced nMFI (p