ArticleExperimental & molecular medicine2019
CDKN2B downregulation and other genetic characteristics in T-acute lymphoblastic leukemia.
Article in Experimental & molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 73 citations in OpenAlex.
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- DNMT3A-R882 mutation promotes acute myeloid leukemia progression by recruiting E2H2 to inhibit circKCNQ5 methylation.Discover oncology · 2025Article
- T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments.Leukemia · 2025Review
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- Clinical characteristics and prognosis of ALL in children with CDKN2A/B gene deletion.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Transcriptomics-based anti-tuberculous mechanism of traditional Chinese polyherbal preparation NiuBeiXiaoHe intermediates.Frontiers in pharmacology · 2024Article
- The Prognostic Effect of CDKN2A/2B Gene Deletions in Pediatric Acute Lymphoblastic Leukemia (ALL): Independent Prognostic Significance in BFM-Based Protocols.Diagnostics (Basel, Switzerland) · 2023Article
- IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023Review
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- Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool.International journal of molecular sciences · 2022Review
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- Prognostic Relevance of DNMT3A, FLT3 and NPM1 Mutations in Syrian Acute Myeloid Leukemia Patients.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Probing altered enzyme activity in the biochemical characterization of cancer.Bioscience reports · 2022Review
- SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia.Science advances · 2022Article
- [The characteristics and prognostic impact of NOTCH1/FBXW7 mutation and CDKN2A/B deletion in adult T-cell acute lymphoblastic leukemia patients].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- Comprehensive Overview of Gene Rearrangements in Childhood T-Cell Acute Lymphoblastic Leukaemia.International journal of molecular sciences · 2021Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We identified principal genetic alterations in 97.1% (99/102) of patients with T-acute lymphoblastic leukemia (T-ALL) using integrative genetic analyses, including massive parallel sequencing and multiplex ligation-dependent probe amplification (MLPA). A total of 133 mutations were identified in the following genes in descending order: NOTCH1 (66.7%), FBXW7 (19.6%), PHF6 (15.7%), RUNX1 (12.7%), NRAS (10.8%), and DNMT3A (9.8%). Copy number alterations were most frequently detected in CDKN2B, CDKN2A, and genes on 9p21.3 in T-ALL (45.1%). Gene expression data demonstrated the downregulation of CDKN2B in most cases of T-ALL, whereas CDKN2A downregulation was mainly restricted to deletions. Additional quantitative methylation analysis demonstrated that CDKN2B downregulation stemmed from deletion and hypermethylation. Analysis of 64 patients with CDKN2B hypermethylation indicated an association with an older age of onset and early T cell precursor ALL, which involved very early arrest of T cell differentiation. Genes associated with methylation and myeloid neoplasms, including DNMT3A and NRAS, were more commonly mutated in T-ALL with CDKN2B hypermethylation. In particular, a CDKN2B biallelic deletion or high methylation level (≥45%), the age of onset, and the GATA3 and SH2B3 mutations were factors associated with a poor prognosis. This study clarifies that one of the most important genetic events in T-ALL, namely, CDKN2B downregulation, occurs mechanistically via deletion and hypermethylation. Different susceptible genetic backgrounds exist based on the CDKN2B downregulation mechanism.
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