title: Low expression of PP2A regulatory subunit B55α is associated with T308 phosphorylation of AKT and shorter complete remission duration in acute myeloid leukemia patients.
abstract: The regulation of protein kinase B (AKT) is a dynamic process that depends on the balance between phosphorylation by upstream kinases for activation and inactivation by dephosphorylation by protein phosphatases. Phosphorylated AKT is commonly found in acute myeloid leukemia (AML) and confers an unfavorable prognosis. Understanding the relative importance of upstream kinases and AKT phosphatase in the activation of AKT is relevant for the therapeutic targeting of this signaling axis in AML. The B55α subunit of protein phosphatase 2A (PP2A) has been implicated in AKT dephosphorylation, but its role in regulating AKT in AML is unknown. We examined B55α protein expression in blast cells derived from 511 AML patients using reverse phase protein analysis. B55α protein expression was lower in AML cells compared with normal CD34+ cells. B55α protein levels negatively correlated with threonine 308 phosphorylation levels. Low levels of B55α were associated with shorter complete remission duration, demonstrating that decreased expression is an adverse prognostic factor in AML. These findings suggest that decreased B55α expression in AML is at least partially responsible for increased AKT signaling in AML and suggests that therapeutic targeting of PP2A could counteract this.
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. pruvolo@mdanderson.org
authors.forename: P P
authors.initials: PP
authors.lastname: Ruvolo
authors.forename: Y H
authors.initials: YH
authors.lastname: Qui
authors.forename: K R
authors.initials: KR
authors.lastname: Coombes
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.forename: V R
authors.initials: VR
authors.lastname: Ruvolo
authors.forename: G
authors.initials: G
authors.lastname: Borthakur
authors.forename: M
authors.initials: M
authors.lastname: Konopleva
authors.forename: M
authors.initials: M
authors.lastname: Andreeff
authors.forename: S M
authors.initials: SM
authors.lastname: Kornblau
mesh_terms: D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000503:physiopathology*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012074:Remission Induction
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2