Our results depicted that targeted BCL-2 and PI3K/AKT inhibition acted synergistically in two human B-ALL cell lines with KMT2A::AFF1 translocation, which matched the findings of other groups who investigated the efficacy of simultaneous BCL-2 and PI3K inhibition in DLBCL, Richter’s syndrome, non-Hodgkin lymphoma (NHL), and AML cells [18,19,20,28]. Here, AFF1 is linked to Richter syndrome.