Molecular analysis of the t(8;14)(q24;q11) chromosomal breakpoint junctions in the T‐cell leukemia line MOLT‐16

Shima-Rich, Elizabeth A.; Harden, Alanna M.; McKeithan, Timothy W.; Rowley, Janet D.; Dı́az, Manuel O.

doi:10.1002/(sici)1098-2264(199712)20:4<363::aid-gcc7>3.0.co;2-#

Cited by 17 publications

(4 citation statements)

References 32 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar translocation, targeting TCRA to the MYC/PVT1 locus, marks ∼2% of human T-ALL (21). Sequencing translocation breakpoints from such T-ALL samples identified cryptic RAG recombination signal sequences at the PVT1 side of the breakpoint and lead to suggestions that they represented illegitimate RAG-mediated events (22). The Pvt1 locus is also frequently targeted by proviral integrations in murine leukemia virus-induced T-cell lymphomas in mice (23) and in rats (24).…”

Section: T-cell Lymphomas Induced By β-Catenin Activation Have Recurrentmentioning

confidence: 99%

β-Catenin induces T-cell transformation by promoting genomic instability

Dose

Emmanuel

Chaumeil

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Deregulated activation of β-catenin in cancer has been correlated with genomic instability. During thymocyte development, β-catenin activates transcription in partnership with T-cell-specific transcription factor 1 (Tcf-1). We previously reported that targeted activation of β-catenin in thymocytes (CAT mice) induces lymphomas that depend on recombination activating gene (RAG) and myelocytomatosis oncogene (Myc) activities. Here we show that these lymphomas have recurring Tcra/Myc translocations that resulted from illegitimate RAG recombination events and resembled oncogenic translocations previously described in human T-ALL. We therefore used the CAT animal model to obtain mechanistic insights into the transformation process. ChIP-seq analysis uncovered a link between Tcf-1 and RAG2 showing that the two proteins shared binding sites marked by trimethylated histone-3 lysine-4 (H3K4me3) throughout the genome, including near the translocation sites. Pretransformed CAT thymocytes had increased DNA damage at the translocating loci and showed altered repair of RAG-induced DNA double strand breaks. These cells were able to survive despite DNA damage because activated β-catenin promoted an antiapoptosis gene expression profile. Thus, activated β-catenin promotes genomic instability that leads to T-cell lymphomas as a consequence of altered double strand break repair and increased survival of thymocytes with damaged DNA.beta-catenin/Tcf-1 | DNA recombination Tcf7 | Ctnnb1

show abstract

Section: T-cell Lymphomas Induced By β-Catenin Activation Have Recurrentmentioning

confidence: 99%

β-Catenin induces T-cell transformation by promoting genomic instability

Dose

Emmanuel

Chaumeil

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In addition, about 40% of T-ALLs harbor chromosomal translocations juxtaposing developmentally important transcription factor oncogenes next to strong regulatory elements located in the vicinity of the T-cell receptor β (TCRB) gene in chromosome 7q34 or the T-cell receptor α-δ (TCRAD) locus in chromosome 14q11 [Ferrando and Look, 2000]. These T-ALL-specific transcription factor oncogenes include basic helix-loop-helix (bHLH) family members such as TAL1 [Begley et al 1989;Bernard et al 1990;Chen et al 1990;Finger et al 1989], TAL2 [Xia et al 1991], LYL1 [Mellentin et al 1989] and BHLHB1 [Wang et al 2000]; LIM-only domain (LMO) proteins such as LMO1 and LMO2 Greenberg et al 1990;McGuire et al 1989;Royer-Pokora et al 1991;Warren et al 1994]; the TLX1/HOX11 [Dube et al 1991;Hatano et al 1991;Kennedy et al 1991] TLX3/HOX11L2, [Hansen-Hagge et al 2002]; NKX2.5 [Nagel et al 2003;Przybylski et al 2006]; and HOXA homeobox genes [Hansen-Hagge et al 2002;Soulier et al 2005]; the MYC [Erikson et al 1986;Inaba et al 1990;Shima-Rich et al 1997;Shima et al 1986;Urashima et al 1992] and MYB [Clappier et al 2007] oncogenes; and TAN1, a truncated and constitutively activated form of the NOTCH1 receptor [Ellisen et al 1991;Palomero et al 2006a]. In some cases, these factors can also be activated in the context of other non-TCR-associated chromosomal abnormalities.…”

Section: Clinical Challenges and Molecular Features Of T-allmentioning

confidence: 99%

The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy

Tosello

Ferrando

2013

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. Small molecule gamma secretase inhibitors (GSIs) can effectively inhibit oncogenic NOTCH1 and are in clinical testing for the treatment of T-ALL. Treatment with GSIs and glucocorticoids are strongly synergistic and may overcome the gastrointestinal toxicity associated with systemic inhibition of the NOTCH pathway. In addition, emerging new anti-NOTCH1 therapies include selective inhibition of NOTCH1 with anti-NOTCH1 antibodies and stapled peptides targeting the NOTCH transcriptional complex in the nucleus.

show abstract

“…The RAG system acts on specific DNA sequences bordering the cassettes (Cortes et al 1996). RAG does not scramble the whole genome although it causes oncogenic translocations between sequences similar to its normal consensus (Shima-Rich et al 1997) and also can mediate transposition of junctional sequences (Hiom et al 1998). The mutagenesis that occurs at joining and later during somatic maturation of antibody genes is likewise focused.…”

Section: The Immune System Ignores the Conceptual Boundaries That Sepmentioning

confidence: 99%

Hereditary stability and variation in evolution and development

Thaler

1999

Evolution and Development

View full text Add to dashboard Cite

SUMMARY Evolution and development are both lineage processes but are often conceptualized as occurring by different and mutually exclusive mechanisms. It is conventionally asserted that evolution occurs via the random generation of diversity and the subsequent survival of those that pass selection. On the other hand, development is too often presented as proceeding via the unfolding of a deterministic program encoded in the DNA sequence. In biology, universal generalizations are rare and dogmas are often wrong for particular cases. Deterministic mechanisms contribute some of the new DNA sequences that subsequently become substrates for natural selection. Conversely, stochastic and selective mechanisms are intrinsic to development, and also to maintenance of the immune, and possibly, nervous systems. Cancer appears to be another process that straddles distinctions between evolutionary and developmental modes of hereditary change and stabilization. DNA sequence changes are an essential feature of many cancers, but there are also aspects of the disease similar to developmental lineage gone awry. The literature suggests that the cellular changes that give rise to cancer occur by mechanisms commonly associated with both evolutionary and developmental lineage pathways.

show abstract

Molecular analysis of the t(8;14)(q24;q11) chromosomal breakpoint junctions in the T‐cell leukemia line MOLT‐16

Cited by 17 publications

References 32 publications

β-Catenin induces T-cell transformation by promoting genomic instability

β-Catenin induces T-cell transformation by promoting genomic instability

The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy

Hereditary stability and variation in evolution and development

Contact Info

Product

Resources

About