Aberrant Nuclear and Loss of PTEN Expression in Acute Myeloid Leukemia
I Gurevich, C Zhao, CC Yin, X Han, P Lin, X Gao, MH Nguyen, E Pan, LJ Medeiros, C Bueso-Ramos, MJ You. UT MD Anderson Cancer Center, Houston, TX
Background: PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a commonly mutated tumor suppressor gene. PTEN regulates the phosphatidylinositol 3-kinase (PI3K) signaling pathway which is frequently dysregulated in acute myeloid leukemia (AML). In addition to expression levels, the subcellular localization of PTEN also plays an important role in regulating PI3K and thus tumorigenesis. PTEN was initially thought to be exclusively located in the cytoplasm. Recent studies, however, have shown that PTEN is also localized and functions differently in nuclei of neuronal, skin, and pancreas, vascular smooth muscle, intestinal mucosa and squamous cell carcinoma cells. However, the expression patterns of PTEN in normal hematopoietic cells and AML have not been well established. In this study, we assessed the expression patterns of PTEN in normal hematopoietic cells, AML cell lines and primary AML cells.
Design: Expression levels of PTEN in 11 AML cell lines were determined by Taqman PCR to quantify RNA levels, and Western blot analysis was performed for protein levels. Formalin fixed and decalcified bone marrow biopsy specimens were assessed by standard immunohistochemical methods for PTEN expression patterns. Bone marrow biopsy specimens from 5 normal and 63 AML cases were analyzed for nuclear and cytoplasmic expression of PTEN.
Results: PTEN was mainly expressed in the cytoplasm of normal bone marrow cells, with relatively high levels in immature (per band stage) myeloid cells, and lowest levels in erythroid cells, megakaryocytes and mature myeloid cells, including neutrophils and band forms. PTEN expression was lost in 4 of 11 (36%) AML cell lines. PTEN expression was highly variable in the 63 primary AML cases. PTEN was mainly cytoplasmic in 17 (27%) AML cases, was equally expressed in cytoplasm and nucleus in 11 (17%), was lost or significantly diminished in 7 (11%), and was predominantly nuclear in 28 (44%) primary AML samples.
Conclusions: RNA and protein expression of PTEN is lost in a subset of AML cell lines. Primary AML frequently shows nuclear PTEN expression. These findings indicate that aberrant nuclear expression and loss of PTEN expression are relatively frequent events in AML, which likely dysregulates PI3K and contributes to AML tumorigenesis.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 165, Tuesday Afternoon