Introduction: Phosphoinositide( PI3K/AKT) signaling is one of the well-known signaling pathway regulating diverse cellular functions. Phosphoinositide-3 kinase( PI3K) can lead the activation of proliferative anti-apoptotic signaling pathways, thus activation of PI3K/AKT pathway results in molecular chemoresistance in various cancers. INPP4B(Inositol polyphosphate 4-phosphatase II) is a protein which terminates PI3K/AKT dependent signaling, and in several cancers, function loss of INPP4B are known to be related to aggressive phenotype. In recent studies in AML, INPP4B emerged as a poor prognostic outcome in AML driving chemoresistance through a novel gain-of-function mechanism independent of its phosphatase functions. Method: We first investigated INPP4B expression in leukemia cell lines, change of INPP4B expression with drugs(daunorubicin, cytarabine) under mono-culture/mesenchymal cell co-culture system. Patients’ bone marrow samples were collected at the time of AML diagnosis. MNCs(mononuclear cells) were separated using Ficoll-Paque from bone marrow aspirates. Then, CD34+ cells were isolated with MACS CD34+ bead. Cell proliferation assays were done after drug treatments, and western blots were used to check the expression of INPP4B. Results: Among various cell lines KG-1, THP cell lines were selected because of their high expression of INPP4B. We confirm the drug actions on both cell lines, and INPP4B expression decreased in KG-1, THP cell line by daunorubicin treatment, however somewhat maintained by cytarabine treatment. Similar decreased expression of INPP4B was found in MSC co-culture condition. Among 8 patients diagnosed as AML, sample of only 4 patients were suitable for the study. Among 4 patients, only one patient’s cells showed high INPP4B expression with decreased INPP4B expression under daunorubicin treatment. The patient who showed higher INPP4B expression is a therapy-related AML patient with FLT3-ITD mutation. Discussion: INPP4B is a new molecule in AML which suggested as an independent poor prognostic value on survival. Different drug response of INPP4B expression to daunorubicin and cytarabine should be further evaluated, which can be a clue to potential mechanism of chemoresistance in leukemia. To verify the clinical implication of INPP4B, more patients’ data should be collected and long term follow-up studies are needed.