ElevatedPIM2gene expression is associated with poor survival of patients with acute myeloid leukemia

Abstract

The PIM2 gene encodes the serine/threonine kinase involved in cell survival and apoptosis. The aim of the study was to evaluate the expression of the PIM2 gene in acute myeloid leukemia (AML) and to examine its role in apoptosis of the blastic cells. We analyzed the PIM2 expression in 148 patients: 91 with AML, 57 with acute lymphoblastic leukemia and 24 healthy controls by Real-Time PCR and Western blot. Inhibition of the PIM2 gene in human leukemic HL60 cell line was performed with RNAi and apoptosis rate was analyzed. Our results indicate that overexpression of PIM2 in AML is associated with low complete remission rate, high-risk cytogenetics, shorter leukemia-free survival, and event-free survival. Cytometric analysis of HL60/PAC-GFP and HL60/PAC-GFP-shPIM2 cells revealed an increase in the number of apoptotic cells after inhibition of PIM2 gene. In summary, the elevated expression of PIM2 in blastic cells is associated with poor prognosis of AML patients and their resistance to induction therapy.

Feedback Activation of SGK3 and AKT Contributes to Rapamycin Resistance by Reactivating mTORC1/4EBP1 Axis via TSC2 in Breast Cancer

“…Besides mTORC1, 4EBP1 can be phosphorylated by several other kinases, including PIM2 and GSK-3β, which are responsible for rapamycin resistance in AML or RCC respectively35, 36. In contrast to these findings, we showed that the mTORC1 activity was required for the re-phosphorylation of 4EBP1, suggesting that the kinases involved in 4EBP1 phosphorylation after rapamycin exposure may be dependent on the tumor type.…”

“…first reported that rapamycin differentially inhibits S6Ks and 4EBP1; specifically, rapamycin persistently represses p70S6K activity but only transiently attenuates 4EBP1 phosphorylation 34. In acute myeloid leukemia (AML), PIM2-mediated 4EBP1 phosphorylation contributes to the limited repression of rapamycin on cell survival35. In renal cell carcinoma (RCC), overexpressed GSK-3β leads to weak inhibition of 4EBP1 phosphorylation by rapamycin and combination of GSK-3β inhibitor and rapamycin remarkably suppressed 4EBP1 phosphorylation and cell proliferation36.…”

Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics

“…PIM1 has two protein isoforms (34 and 44ΚDa), both containing a proline-rich N-terminal motif that binds to the ETΚ-SH3 domain and is recruited to cell membranes. PIM2 has there protein isoforms (34,37, and 40 KDa), but interestingly, only one protein subtype has been detected for the PIM3 transcript [4]. In human cells, the PIM2 kinase has only two isoforms (34 and 41ΚDa), but in mice there are there (34,37, and 40ΚDa), and the 34KDa isoform has been the main focus of many studies because it plays a crucial role in tumor progression.…”

Expression of the PIM2 gene is associated with more aggressive clinical course in patients with chronic lymphocytic leukemia

“…Their elevated expression has been observed in solid tumors and hematological malignancies. 6,13 The activation of PIM kinases modulates a broad range of cellular phenomena, including apoptosis, progression of the cell cycle, differentiation, protein translation, and interactions with PIM2 kinase attracted particular attention for the research on the biology of CLL cells. The serine/threonine kinase PIM2 is an oncogenic factor that has been shown to promote cell survival by activating the expression of NFκ B-dependent gene expression following a number of proliferation-inducing signals.…”

“…4 Elevated expression of the PIM2 gene was revealed in cell lines derived from human solid (SW480, A549, G361) and hematological tumors (HL60, K562, RAIJ), acute myeloid leukemia, as well as lymphoid malignant cells. 5,6 This indicates a possibility of this factor playing a significant role in neoplastic growth pathogenesis. [7][8][9] In previous studies, increased expression of the PIM2 gene in CLL and follicular and large-cell lymphoma was found.…”