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

Kapelko-Słowik, Katarzyna; Dybko, Jarosław; Grzymajło, Krzysztof; Jaźwiec, Bożena; Urbaniak-Kujda, Donata; Słowik, Mirosław; Potoczek, S; Wołowiec, Dariusz

doi:10.17219/acem/90771

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…This elevated expression of PIM2 is associated with poor prognoses in ALL patients, resulting from an increased resistance in leukemic cells to apoptosis, and its clinical significance is associated with low completeremission rates, shorter leukemia-free survival times, higher-risk cytogenetics, and shorter event-free survival times [34]. In CLL patients, PIM2 expression was also higher than in controls, and this was associated with a more rapid lymphocyte-doubling time, and the proportion of malignant lymphocytes [35]. PIM2 has been shown to interact with PML-RARα (promyelocytic leukemia/retinoic acid receptor alpha), an association which may induce AML-like diseases, as transplanted PIM2-PML-RARα bone marrow cells induced an AML-like disease in mice, and their spleen cells expressed both PIM2 and PML-RARα [36].…”

Section: Leukemiamentioning

confidence: 99%

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

Wang¹,

Xiu²,

Ren³

et al. 2021

J. Cancer

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PIM2 (proviral integration site for Moloney murine leukemia virus 2) kinase plays an important role as an oncogene in multiple cancers, such as leukemia, liver, lung, myeloma, prostate and breast cancers. PIM2 is largely expressed in both leukemia and solid tumors, and it promotes the transcriptional activation of genes involved in cell survival, cell proliferation, and cell-cycle progression. Many tumorigenic signaling molecules have been identified as substrates for PIM2 kinase, and a variety of inhibitors have been developed for its kinase activity, including SMI-4a, SMI-16a, SGI-1776, JP11646 and DHPCC-9. Here, we summarize the signaling pathways involved in PIM2 kinase regulation and PIM2 mechanisms in various neoplastic diseases. We also discuss the current status and future perspectives for the development of PIM2 kinase inhibitors to combat human cancer, and PIM2 will become a therapeutic target in cancers in the future.

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Section: Leukemiamentioning

confidence: 99%

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

Wang¹,

Xiu²,

Ren³

et al. 2021

J. Cancer

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Section: Discussionmentioning

confidence: 99%

“…Thus, the relationship between MKP-1 and m6A modification in TNBC would be worth exploration in the future. PIM2 is a oncogene that have been validated in breast, liver cancer and chronic lymphocytic leukemia (48,49). Tingting Yang et al demonstrated that PIM2 mediated phosphorylation of HSF1 at Thr120 to regulate HSF1 protein stability, and induce PD-L1 expression in breast cancer, which suggested that it might affect immune therapy response (50).…”

Section: Discussionmentioning

confidence: 99%

Identification of m6A modification patterns and development of m6A–hypoxia prognostic signature to characterize tumor microenvironment in triple-negative breast cancer

Shi

Zhong

et al. 2022

Front. Immunol.

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BackgroundN6-methylation (m6A) modification of RNA has been found to have essential effects on aspects of the tumor microenvironment (TME) including hypoxia status and mobilization of immune cells. However, there are no studies to explore the combined effect of m6A modification and hypoxia on molecular heterogeneity and TME of triple-negative breast cancer (TNBC).MethodsWe collected The Cancer Genome Atlas (TCGA-TNBC, N=139), the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC-TNBC, N=297), the GSE103091, GSE21653, and GSE135565 series from the Gene Expression Omnibus (GEO-TNBC, N=247), and FUSCCTNBC (N=245) for our study. The non-negative matrix factorization algorithm was used to cluster TNBC samples. Immune cell infiltration was analyzed by the CIBERSORT algorithm. The enrichment scores were calculated by single-sample gene set enrichment analysis(ssGSEA) to characterize TME in TNBC samples. Immunohistochemistry (IHC) and qRT-PCR were performed to detect the gene expression.ResultsBased on the expression of m6A-related genes, we identified three distinct m6A clusters (denoted A, B, and C) in TNBC samples. Comparing the TME characteristics among the three clusters, we observed that cluster C was strongly related to hypoxia status and immune suppression, whereas clusters A and B displayed more immune cell infiltration. Therefore, we combine m6A and hypoxia related genes to classify two m6A-hypoxia clusters of TNBC and screened six prognostic genes by LASSO-Cox regression to construct a m6A-hypoxia signature(MHPS), which divided TNBC samples into high- and low-risk groups. We identified different TME features, immune cell infiltration between the two groups, and a better immunotherapy response was observed in the low-risk group. A nomogram was constructed with tumor size, lymph node, and risk score to improve clinical application of MHPS.ConclusionWe identified distinct TME characteristics of TNBC based on three different m6A modification patterns. Then, we constructed a specific m6A–hypoxia signature for TNBC to evaluate risk and predict immunotherapy response of patients, to enable more accurate treatment in the future.

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“…Studies have confirmed over-expression of Pim-1 and Pim-2 in CLL patients compared to normal lymphocytes [124,125]. Pim-1/− 2 are especially elevated in B-CLL patients and correlated with worse prognosis in B-CLL (elevated in Binet stage C) and B-CLL subtype, while Pim-1/2 expression was lower in patients achieving complete remission [126][127][128][129]. Pim-3 did not correlate with any clinical characteristic.…”

Section: Multiple Myeloma (Mm)mentioning

confidence: 93%

Targeting Pim kinases in hematological cancers: molecular and clinical review

Bellon

Nicot

2023

Mol Cancer

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Decades of research has recognized a solid role for Pim kinases in lymphoproliferative disorders. Often up-regulated following JAK/STAT and tyrosine kinase receptor signaling, Pim kinases regulate cell proliferation, survival, metabolism, cellular trafficking and signaling. Targeting Pim kinases represents an interesting approach since knock-down of Pim kinases leads to non-fatal phenotypes in vivo suggesting clinical inhibition of Pim may have less side effects. In addition, the ATP binding site offers unique characteristics that can be used for the development of small inhibitors targeting one or all Pim isoforms. This review takes a closer look at Pim kinase expression and involvement in hematopoietic cancers. Current and past clinical trials and in vitro characterization of Pim kinase inhibitors are examined and future directions are discussed. Current studies suggest that Pim kinase inhibition may be most valuable when accompanied by multi-drug targeting therapy.

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

Abstract: The study was financially supported by the statutory funds of Wroclaw Medical University (ST.A080.17.035).

Cited by 5 publications

References 24 publications

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

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

Identification of m6A modification patterns and development of m6A–hypoxia prognostic signature to characterize tumor microenvironment in triple-negative breast cancer

Targeting Pim kinases in hematological cancers: molecular and clinical review

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