Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript.

Begley, C. Glenn; Aplan, PD; Davey, Michael P.; Nakahara, Kenneth; Tchorz, Kathryn M.; Kurtzberg, Joanne; Hershfield, Michael S.; Haynes, B F; Di, Cohen; Waldmann, Thomas A.; Kirsch, Ilan R.

doi:10.1073/pnas.86.6.2031

Cited by 261 publications

(143 citation statements)

References 40 publications

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“…The TAL1 (or SCL) gene was originally identi®ed from its involvement by a recurrent chromosomal translocation in patients with T-cell acute lymphoblastic leukemia (T-ALL) (Begley et al, 1989a;Chen et al, 1990;Finger et al, 1989). Interstitial deletions that fuse TAL1 coding sequences to the promoter of an upstream gene, SIL (for SCL interrupting locus), were found subsequently to occur with greater frequency than translocations (Aplan et al, 1990;Bernard et al, 1990;Brown et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

et al. 1999

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Section: Introductionmentioning

confidence: 99%

p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

et al. 1999

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“…[34][35][36][37][38][39][40][41][42][43][44] However, it has recently been shown that aberrant overexpression of T-ALL oncogenes can occur in the absence of chromosomal translocation. 45 In order to characterize the expression of T-ALL oncogenes, such as scl, lmo1, lmo2, hox11, tlx3a and tlx3b in NOTCH1-induced T-cell leukemias, RT-PCR analysis was performed using oncogene-specific primers with RNA from FACS-sorted GFP-positive leukemic cells.…”

Section: Expression Of Other Known T-all Oncogenes In Notch1-induced mentioning

confidence: 99%

NOTCH1-induced T-cell leukemia in transgenic zebrafish

et al. 2007

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Activating mutations in the NOTCH1 gene have been found in about 60% of patients with T-cell acute lymphoblastic leukemia (T-ALL). In order to study the molecular mechanisms by which altered Notch signaling induces leukemia, a zebrafish model of human NOTCH1-induced T-cell leukemia was generated. Seven of sixteen mosaic fish developed a T-cell lymphoproliferative disease at about 5 months. These neoplastic cells extensively invaded tissues throughout the fish and caused an aggressive and lethal leukemia when transplanted into irradiated recipient fish. However, stable transgenic fish exhibited a longer latency for leukemia onset. When the stable transgenic line was crossed with another line overexpressing the zebrafish bcl2 gene, the leukemia onset was dramatically accelerated, indicating synergy between the Notch pathway and the bcl2-mediated antiapoptotic pathway. Reverse transcription-polymerase chain reaction analysis showed that Notch target genes such as her6 and her9 were highly expressed in NOTCH1-induced leukemias. The ability of this model to detect a strong interaction between NOTCH1 and bcl2 suggests that genetic modifier screens have a high likelihood of revealing other genes that can cooperate with NOTCH1 to induce T-ALL.

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“…[1][2][3][4] Genomic rearrangements of the SCL gene have been reported in approximately 30% of patients with paediatric T-ALL 5,6 and it has been suggested that additional mechanisms may be responsible for ectopic expression in a further 30% of these patients. 4 Transgenic studies in mice have also shown Correspondence: AR Green; Fax: 44 01223 336827 Received 4 September 1998; accepted 20 February 1999 that ectopic expression of SCL in thymocytes gives rise to T cell tumours.…”

Section: Introductionmentioning

confidence: 99%

Chromatin structure and transcriptional regulation of the stem cell leukaemia (SCL) gene in mast cells

Göttgens

McLaughlin

et al. 1999

Leukemia

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The stem cell leukaemia (SCL) gene is a member of the basic helix-loop-helix family of transcription factors and is essential for the development of all haematopoietic lineages. SCL is expressed in pluripotent haematopoietic stem cells and also following commitment to the erythroid, mast and megakaryocytic lineages. The mechanisms responsible for this pattern of expression are poorly understood, but are likely to illuminate the molecular basis for stem cell development and lineage commitment. Here we present the first description of the regulation of the SCL gene in mast cells. In this study we systematically analysed the chromatin structure of a 45 kb region of the murine SCL locus in mast cells. The pattern of DNase 1 and restriction endonuclease hypersensitive sites in mast cells was distinct from, but overlapped with, the pattern previously described in erythroid and primitive myeloid cells. Each potential regulatory element was tested using transient reporter assays to assess their functional significance in mast cells. These studies identified two potent enhancers, one of which was downstream of the SCL gene. Further characterisation of this 3Ј enhancer demonstrated that it required the presence of two distinct DNase 1 hypersensitive sites for full activity, and that it was capable of stimulating transcription from both promoter 1a and 1b. Since the 3Ј enhancer is active in both erythroid and mast cells, it will now be important to see whether it is independently activated in these lineages, or whether it is also active in haematopoietic stem cells.

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Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript.

Abstract: We have studied a leukemic stem-cell line,

Cited by 261 publications

References 40 publications

p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

NOTCH1-induced T-cell leukemia in transgenic zebrafish

Chromatin structure and transcriptional regulation of the stem cell leukaemia (SCL) gene in mast cells

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