In the present study, we aimed to investigate the anti-leukemic property of small molecule inhibitor of c-Myc 10058-F4 in two distinct acute leukemia cell lines consist of acute promyelocytic leukemia (APL)-derived NB4 cells (with wild-type PTEN) and acute lymphoblastic leukemia (ALL)-derived Nalm-6 cells (with down-regulated PTEN).
Downregulation of MCL-1 by BEZ235 further contributed to the modulation of dexamethasone resistance by increasing the amount of BIM available to induce apoptosis, especially in PTEN-null T-ALL where inhibition of AKT only partially overcame AKT-induced BIM suppression.
Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.
We report that inhibition of PI3K/Akt, either by the PI3K inhibitor Ly294002 or by expression of PTEN, synergized the ability of the MDM2 antagonist nutlin-3 to induce apoptosis in acute lymphoblastic leukemia (ALL).
Examining the cellular localization of MDM2, we confirmed that the majority of MDM2 is localized in the nucleus in PTEN-negative doxorubicin-sensitive ALL cells, whereas MDM2 is expressed predominantly in the cytoplasm in either PTEN-positive or PTEN-transfected cells.