ArticleLeukemia2015
Activation of the PI3K/AKT pathway by microRNA-22 results in CLL B-cell proliferation.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of the Prognostic Value of microRNA-22 in Leukemia Patients.Technology in cancer research & treatmentPooled it
- Ibrutinib therapy downregulates AID enzyme and proliferative fractions in chronic lymphocytic leukemia.Blood · 2019Trial
- miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study.Haematologica · 2017Trial
- Early-onset CLL is characterized by enhanced microenvironment-driven metabolic fitness, increased proliferative bias, and accelerated disease progression.Frontiers in immunology · 2026Article
- Unveiling the role of microRNAs, the PI3K/AKT pathway, and their associations in various types of leukemia: a comprehensive review.Blood research · 2025Review
- The Role of MicroRNAs, CircRNAs, and LncRNAs in Chronic Lymphocytic Leukemia.Current pharmaceutical design · 2025Review
- MicroRNA Profiling as a Predictive Indicator for Time to First Treatment in Chronic Lymphocytic Leukemia: Insights from the O-CLL1 Prospective Study.Non-coding RNA · 2024Article
- Genetic Changes in Mastocytes and Their Significance in Mast Cell Tumor Prognosis and Treatment.Genes · 2024Review
- The emerging role of microRNA-22 in the Leukemia: experimental and clinical implications.Molecular biology reports · 2023Review
- Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation.Cancers · 2023Review
- The discrete roles of individual FOXO transcription factor family members in B-cell malignancies.Frontiers in immunology · 2023Review
- Hsa-miR-22-3p inhibits liver cancer cell EMT and cell migration/ invasion by indirectly regulating SPRY2.PloS one · 2023Article
- Article
- miRNAs in Lymphocytic Leukaemias-The miRror of Drug Resistance.International journal of molecular sciences · 2022Review
- TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression.Cancers · 2022Article
- Bioinformatic Analysis Reveals Hub Immune-Related Genes of Diabetic Foot Ulcers.Frontiers in surgery · 2022Article
- Small molecules with huge impacts: the role of miRNA-regulated PI3K pathway in human malignancies.Molecular biology reports · 2021Review
- MicroRNA‑93 knockdown inhibits acute myeloid leukemia cell growth via inactivating the PI3K/AKT pathway by upregulating DAB2.International journal of oncology · 2021Article
- Article
- Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal B cells arrested in G0/G1 stages that coexist, in different proportions, with proliferative B cells. Understanding the crosstalk between the proliferative subsets and their milieu could provide clues on CLL biology. We previously identified one of these subpopulations in the peripheral blood from unmutated patients that appears to be a hallmark of a progressive disease. Aiming to characterize the molecular mechanism underlying this proliferative behavior, we performed gene expression analysis comparing the global mRNA and microRNA expression of this leukemic subpopulation, and compared it with their quiescent counterparts. Our results suggest that proliferation of this fraction depend on microRNA-22 overexpression that induces phosphatase and tensin homolog downregulation and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. Transfection experiments demonstrated that miR-22 overexpression in CLL B cells switches on PI3K/AKT, leading to downregulation of p27(-Kip1) and overexpression of Survivin and Ki-67 proteins. We also demonstrated that this pathway could be triggered by microenvironment signals like CD40 ligand/interleukin-4 and, more importantly, that this regulatory loop is also present in lymph nodes from progressive unmutated patients. Altogether, these results underline the key role of PI3K/AKT pathway in the generation of the CLL proliferative pool and provide additional rationale for the usage of PI3K inhibitors.
Indexed as
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.