ArticleLeukemia2010
Reduced expression of the tumor suppressor PHLPP1 enhances the antiapoptotic B-cell receptor signal in chronic lymphocytic leukemia B-cells.
Article in Leukemia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
19 citing papers in PubMed, 28 citations in OpenAlex.
- Combinatorial DNMTs and EZH2 inhibition reprograms the H3K27me3 and DNAme-mediated onco-epigenome to suppress multiple myeloma proliferation.Scientific reports · 2025Article
- Inflammation as a driver of hematological malignancies.Frontiers in oncology · 2024Review
- PHLPP Signaling in Immune Cells.Current topics in microbiology and immunology · 2022Review
- Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer.Cell death & disease · 2021Article
- The Multifaceted Role of CMA in Glioma: Enemy or Ally?International journal of molecular sciences · 2021Review
- Detection of selection signatures for response to Aleutian mink disease virus infection in American mink.Scientific reports · 2021Article
- PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling.Annual review of pharmacology and toxicology · 2021Review
- Mechanisms of B Cell Receptor Activation and Responses to B Cell Receptor Inhibitors in B Cell Malignancies.Cancers · 2020Review
- Tumor Suppressors in Chronic Lymphocytic Leukemia: From Lost Partners to Active Targets.Cancers · 2020Review
- Importance of Crosstalk Between Chronic Lymphocytic Leukemia Cells and the Stromal Microenvironment: Direct Contact, Soluble Factors, and Extracellular Vesicles.Frontiers in oncology · 2020Review
- Review
- Targeted activation of the SHP-1/PP2A signaling axis elicits apoptosis of chronic lymphocytic leukemia cells.Haematologica · 2017Article
- Oncogenic Ras differentially regulates metabolism and anoikis in extracellular matrix-detached cells.Cell death and differentiation · 2016Article
- "Role of the B-cell receptor and the microenvironment in chronic lymphocytic leukemia''.Blood cancer journal · 2013Article
- Antibody-based therapeutics for the treatment of human B cell malignancies.Current allergy and asthma reports · 2013Review
- Suppression of survival signalling pathways by the phosphatase PHLPP.The FEBS journal · 2013Article
- Mechanisms and consequences of the loss of PHLPP1 phosphatase in chronic lymphocytic leukemia (CLL).Leukemia · 2012Article
- Article
- Novel Agents and Emerging Strategies for Targeting the B-Cell Receptor Pathway in CLL.Mediterranean journal of hematology and infectious diseases · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PI3K/Akt pathway is activated in response to various microenvironmental stimuli that regulate the survival and proliferation of chronic lymphocytic leukemia (CLL) B-cells, including triggering of the B-cell receptor (BCR). Although this pathway is frequently targeted in cancer, no significant alterations have yet been identified in CLL. We now show that the phosphatase PH domain leucin-rich repeat protein phosphatase (PHLPP1), a recently identified tumor suppressor and negative regulator of the Akt kinase, is absent or expressed at substantially reduced levels in CLL B-cells. To determine what the consequences of PHLPP1 loss on BCR signaling are, we downregulated or re-expressed PHLPP1 in lymphoma cell lines and primary CLL B-cells, respectively. Downregulation of PHLPP1 increased BCR-induced phosphorylation and activation of the Akt, GSK3 and ERK kinases, whereas re-expression had the opposite effect. Importantly, re-expression of PHLPP1 in primary CLL cells prevented upregulation of Mcl-1 and inhibited the increase in leukemic cell viability induced by sustained BCR engagement. Enforced expression of PHLPP1 also affected the response to other microenvironmental stimuli, particularly in terms of ERK phosphorylation. Collectively, these data show that CLL cells lack an important negative regulator of the Akt and ERK pathways, which could confer them a growth advantage by facilitating the propagation of crucial microenvironment-derived stimuli.
Indexed as
Identifiers
What OpenQuestion holds
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.