<i>Tcrδ</i>translocations that delete the<i>Bcl11b</i>haploinsufficient tumor suppressor gene promote atm-deficient T cell acute lymphoblastic leukemia

Ehrlich, Lori A.; Yang-Iott, Katherine; Bassing, Craig H.

doi:10.4161/15384101.2014.949144

Cited by 10 publications

(6 citation statements)

References 43 publications

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“…Despite the lack of t(12;14), both Cd-negative (497 and 745) tumors displayed hemizygous deletion of chromosome 12 telomeric regions, supporting the existence of potential tumor-suppressor genes (eg, Bcl11b). 3,[14][15][16] In this context, SKY analyses identified t(12;15) translocations involving chromosome 15 in tumor 745 ( Figure 2B and supplemental Figure 2C). Finally, CGH also indicated that murine ATM 2/2 thymic lymphomas, regardless of Ed status, display genetic changes that have been associated with human T-cell acute lymphoblastic leukemia (T-ALL), including trisomy of chromosome 15 containing c-Myc, amplification and overexpression of Notch1, deletion of Pten, and overexpression of IL7R ( Figure 2F), highlighting ATM-deficient murine thymic lymphomas as a bona fide animal model for human T-ALL.…”

Section: Resultsmentioning

confidence: 99%

Aberrant TCRδ rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency

Jiang

Lee

et al. 2015

Blood

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Section: Resultsmentioning

confidence: 99%

Aberrant TCRδ rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency

Jiang

Lee

et al. 2015

Blood

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“…BCL11B encodes a zinc finger transcription factor that is mutated and deleted in mouse thymic lymphomas induced by γ-radiation (Wakabayashi et al 2003a) and in T-ALL tumors arising in Atm-deficient (Ehrlich et al 2014) and TLX1 transgenic mice (De Keersmaecker et al 2010). In human T-ALL, BCL11B mutations are present in ∼10% of cases (De Keersmaecker et al 2010;Gutierrez et al 2011), frequently in combination with TLX1 and TLX3 translocations (Liu et al 2017).…”

Section: Bcl11bmentioning

confidence: 99%

The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia

Gianni

Belver

Ferrando

2019

Cold Spring Harb Perspect Med

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from early T-cell progenitors. The recognition of clinical, genetic, transcriptional, and biological heterogeneity in this disease has already translated into new prognostic biomarkers, improved leukemia animal models, and emerging targeted therapies. This work reviews our current understanding of the molecular mechanisms of T-ALL.

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“…For example, Dik et al () showed that removal of a negative regulatory element from the LMO2 locus is the main mechanism underlying the activation of this gene by the t(11;14)(p13;q11). Furthermore, TCR translocations may actually, albeit rarely, instead lead to silencing of a gene, as shown for BCL11B and LEF1 ; these two genes are otherwise relatively often targeted by deletions or inactivating mutations in T‐ALL (Gutierrez et al, 2010b, 2011; Le Noir et al, ; Ehrlich et al, ).…”

Section: Genetics Of T‐allmentioning

confidence: 99%

Pediatric T‐cell acute lymphoblastic leukemia

Karrman

Johansson

2016

Genes Chromosomes & Cancer

105

111

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The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T‐cell ALL (T‐ALL) comprises 10–15% of cases. T‐ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes, such as differentiation, self‐renewal capacity, proliferation, and apoptosis, are targeted and deranged by several types of neoplasia‐associated genetic alteration, for example, translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription. Epigenetically, T‐ALL is characterized by gene expression changes caused by hypermethylation of tumor suppressor genes, histone modifications, and miRNA and lncRNA abnormalities. Although some genetic and gene expression patterns have been associated with certain clinical features, such as immunophenotypic subtype and outcome, none has of yet generally been implemented in clinical routine for treatment decisions. The recent advent of massive parallel sequencing technologies has dramatically increased our knowledge of the genetic blueprint of T‐ALL, revealing numerous fusion genes as well as novel gene mutations. The challenges now are to integrate all genetic and epigenetic data into a coherent understanding of the pathogenesis of T‐ALL and to translate the wealth of information gained in the last few years into clinical use in the form of improved risk stratification and targeted therapies. Here, we provide an overview of pediatric T‐ALL with an emphasis on the acquired genetic alterations that result in this disease. © 2016 Wiley Periodicals, Inc.

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Tcrδtranslocations that delete theBcl11bhaploinsufficient tumor suppressor gene promote atm-deficient T cell acute lymphoblastic leukemia

Cited by 10 publications

References 43 publications

Aberrant TCRδ rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency

Aberrant TCRδ rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency

The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia

Pediatric T‐cell acute lymphoblastic leukemia

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