Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia

Krieger, David; Moericke, Anja; Oschlies, Ilske; Zimmermann, Martin; Schrappe, Martin; Reiter, Alfred; Burkhardt, Birgit

doi:10.3324/haematol.2009.007526

Cited by 31 publications

(24 citation statements)

References 22 publications

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“…Consistently, loss of heterozygosity at the short arm of chromosome 9 has been associated with a favorable initial treatment response in pediatric T-ALL patients treated in the Berlin-Frankfurt-Munster ALL-95 study protocol. 41 Activation of NOTCH signaling through NOTCH1 and/or FBXW7 mutations has been associated with a favorable prognosis in several, but not all, pediatric study protocols. [42][43][44][45] Similarly, controversial results on the prognostic effect of NOTCH activation have been obtained in adult T-ALL.…”

Section: Discussionmentioning

confidence: 99%

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia

Vlierberghe

Ambesi-Impiombato

Keersmaecker

et al. 2013

Blood

137

119

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Adult T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic tumor associated with poor outcome. In this study, we analyzed the prognostic relevance of genetic alterations, immunophenotypic markers, and microarray gene expression signatures in a panel of 53 adult T-ALL patients treated in the Eastern Cooperative Oncology Group E2993 clinical trial. An early immature gene expression signature, the absence of bi-allelic TCRG deletion, CD13 surface expression, heterozygous deletions of the short arm of chromosome 17, and mutations in IDH1/IDH2 and DNMT3A genes are associated with poor prognosis in this series. In contrast, expression of CD8 or CD62L, homozygous deletion of CDKN2A/CDKN2B, NOTCH1 and/or FBXW7 mutations, and mutations or deletions in the BCL11B tumor suppressor gene were associated with improved overall survival. Importantly, the prognostic relevance of CD13 expression and homozygous CDKN2A/CDKN2B deletions was restricted to cortical and mature T-ALLs. Conversely, mutations in IDH1/IDH2 and DNMT3A were specifically associated with poor outcome in early immature adult T-ALLs. This trial was registered at www.clinicaltrials.gov as #NCT00002514

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Section: Discussionmentioning

confidence: 99%

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia

Vlierberghe

Ambesi-Impiombato

Keersmaecker

et al. 2013

Blood

137

119

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“…NOTCH1 mutations were not generally associated with a reduced incidence of deletions or LOH. The incidence of LOH of chromosome 9p at the locus of CDKN2A and CDKN2B, which has been investigated previously, 36 (Table 3).…”

Section: Notch1/fbxw7 and Loh6qmentioning

confidence: 99%

Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence

Bonn

Rohde

Zimmermann

et al. 2013

Blood

111

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Key Points• Confirms the prognostic effect of NOTCH1 mutations in pediatric T-cell lymphoblastic lymphoma in a large and independent cohort. • Provides the scientific basis for using NOTCH1 mutations and chromosome 6q alterations as stratification criterion in patients with T-cell lymphoblastic lymphoma.Probability of event-free survival (pEFS) in pediatric T-cell lymphoblastic lymphoma is about 80%, whereas survival in relapsed patients is very poor. No stratification criteria have been established so far. Recently, activating NOTCH1 mutations were reported to be associated with favorable prognosis, and loss of heterozygosity at chromosome 6q (LOH6q) was reported to be associated with increased relapse risk. The current project was intended to evaluate the prognostic effect of these markers. Mutations in hot spots of NOTCH1 and FBXW7 were analyzed in 116 patients. Concerning LOH6q status, 118 patients were investigated, using microsatellite marker analysis, in addition to an earlier reported cohort of 99 available patients. Ninety-two cases were evaluable for both analyses. All patients were treated with T-cell lymphoblastic lymphoma-Berlin-Frankfurt-Münster group (BFM)-type treatment. LOH6q was observed in 12% of patients (25/217) and associated with unfavorable prognosis (pEFS 27% 6 9% vs 86% 6 3%; P < .0001). In 60% (70/116) of the patients, NOTCH1 mutations were detected and associated with favorable prognosis (pEFS 84% 6 5% vs 66% 6 7%; P = .021). Interestingly, NOTCH1 mutations were rarely observed in patients with LOH in 6q16. Both prognostic markers will be used as stratification criteria in coming Non-Hodgkin Lymphoma-BFM trials. (Blood. 2013;121(16):3153-3160)

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“…The prognostic implications of loss of heterozygosity at the short arm of chromosome 9 were evaluated in pediatric T-ALL patients treated according to the Berlin-Frankfurt-Munster regimen (60). This study showed that loss of heterozygosity at 9p was associated with a favorable initial treatment response in T-ALL (60).…”

Section: Alterations In Cell Cycle Regulatorsmentioning

confidence: 99%

The molecular basis of T cell acute lymphoblastic leukemia

Vlierberghe¹,

Ferrando²

2012

J. Clin. Invest.

439

395

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T cell acute lymphoblastic leukemias (T-ALLs) arise from the malignant transformation of hematopoietic progenitors primed toward T cell development, as result of a multistep oncogenic process involving constitutive activation of NOTCH signaling and genetic alterations in transcription factors, signaling oncogenes, and tumor suppressors. Notably, these genetic alterations define distinct molecular groups of T-ALL with specific gene expression signatures and clinicobiological features. This review summarizes recent advances in our understanding of the molecular genetics of T-ALL.

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Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia

Cited by 31 publications

References 22 publications

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia

Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence

The molecular basis of T cell acute lymphoblastic leukemia

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