INPP4B is catalytically active but not coupled to pAKT^S473 inhibition in AML. Immunoblotting analysis of INPP4B and pAKT^S473 in (A) AML cell lines and (B) CD34⁺ sorted progenitors derived from normal donors relative to the INPP4B-expressing OCI-AML3 cell line. (C) Analysis of INPP4B and pAKT^S473 in patient-derived AML samples relative to OCI-AML3 cells and normal BM. (D) Cell lysates from OCI-AML3 cells were immunodepleted with INPP4A antibody (Ab) to demonstrate removal of INPP4A protein in lysates prior to performing INPP4B enzymatic assays. (E) Endogenous INPP4B expression in primary AML samples relative to PtdIns(3,4)P₂ 4-phosphatase activity. Lysates were immunodepleted of INPP4A and the capacity for INPP4B to process PtdIns(3,4)P₂ and release free phosphate ions (Pi) quantified by a malachite green reporter assay. Results represent the mean ± standard deviation (SD) of 2 independent experiments.