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MRD post therapy has been incorporated into risk stratification and clinical management, resulting in substantially improved outcomes in pediatric and adult patients. Currently, MRD in B\u2010ALL is most commonly assessed by multiparametric flow cytometry and molecular (polymerase chain reaction or high\u2010throughput sequencing based) methods. The detection of MRD by flow cytometry in B\u2010ALL often begins with B cell antigen\u2010based gating strategies. Over the past several years, targeted immunotherapy directed against B cell markers has been introduced in patients with relapsed or refractory B\u2010ALL and has demonstrated encouraging results. However, targeted therapies have significant impact on the immunophenotype of leukemic blasts, in particular, downregulation or loss of targeted antigens on blasts and normal B cell precursors, posing challenges for MRD detection using standard gating strategies. 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