ArticleOncotarget2014
Low PKCα expression within the MRD-HR stratum defines a new subgroup of childhood T-ALL with very poor outcome.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- FZD6 triggers Wnt-signalling driven by WNT10BHematological oncology · 2021Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia.Cancer discovery · 2020Article
- Protein Kinase C Quality Control by Phosphatase PHLPP1 Unveils Loss-of-Function Mechanism in Cancer.Molecular cell · 2019Article
- USP7 Cooperates with NOTCH1 to Drive the Oncogenic Transcriptional Program in T-Cell Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Crosstalk between PKCα and PI3K/AKT Signaling Is Tumor Suppressive in the Endometrium.Cell reports · 2018Article
- Shining a light on cell signaling in leukemia through proteomics: relevance for the clinic.Expert review of proteomics · 2018Review
- Protein kinase C: perfectly balanced.Critical reviews in biochemistry and molecular biology · 2018Review
- Reversing the Paradigm: Protein Kinase C as a Tumor Suppressor.Trends in pharmacological sciences · 2017Review
- Phosphoproteomic analysis reveals hyperactivation of mTOR/STAT3 and LCK/Calcineurin axes in pediatric early T-cell precursor ALL.Leukemia · 2017Article
- Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.Scientific reports · 2016Article
- CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia.Oncotarget · 2016Article
- A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation.Oncotarget · 2015Article
- EZH2 is increased in paediatric T-cell acute lymphoblastic leukemia and is a suitable molecular target in combination treatment approaches.Journal of experimental & clinical cancer research : CR · 2015Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) outcome has improved in the last decades, yet one patient in every four still relapses. Except treatment response and immunophenotype, few markers are reliably prognostic in pediatric T-ALL patients. Aiming to improve T-ALL risk stratification, we investigated a new candidate biomarker with potential prognostic relevance. A phosphoproteomic screening of 98 pediatric T-ALL samples at diagnosis had been performed using the high-throughput Reverse Phase Protein Arrays technique, which led to the identification of PKCαS657 as an activated protein with a broad variation among T-ALL samples. To evaluate PKCα potential as a prognostic biomarker, PKCα expression was analyzed using RQ-PCR in a cohort of 173 patients, representative of ALL2000-ALLR2006 AIEOP study. A threshold of PKCα expression with the highest discrimination for incidence of relapse was identified. Patients with PKCα down-regulation, compared to patients with PKCα levels above the threshold, presented a markedly increased cumulative incidence of relapse (43.8% vs. 10.9%, P<0.001), as well as a worse 4-year overall survival (66% vs. 87.9%, P=0.002) and event-free survival (53.1% vs. 85.2%, P=0.002). In particular, low PKCα expression identified cases with extremely poor outcome within the high-risk minimal residual disease (MRD) stratum, their incidence of relapse being of 69% vs. 15% in the high PKCα levels group. In a multivariate analysis adjusting for main prognostic features, PKCα proved to be an independent prognostic factor related to incidence of relapse. Very high risk patients within the high-risk MRD stratum, identified by PKCα expression, could be proposed for experimental therapeutic protocols.
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