Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation

Golub, Todd R.; Barker, George; Lovett, Michael; Gilliland, D. Gary

doi:10.1016/0092-8674(94)90322-0

Cited by 1,128 publications

(734 citation statements)

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“…Full length TEL/PDGFRb cDNA inserted into the pSRa/ MSV/TK/neo retroviral expressing vector was described previously (Golub et al, 1994). The dominant-interfering mutants pcDNA3-FLAG-MKK4 Ala, pCEV29N19RhoA, pCEV29N17Rac1, pCEV29N17Cdc42H, and pCMV5-MEKK (K432A) have also been described .…”

Section: Vectorsmentioning

confidence: 99%

“…The TEL/PDGFRb (T/P) is a chimeric oncogene formed by the chromosomal translocation t(5;12) that fuses the amino terminus of TEL to the transmembrane and cytoplasmic domains of the platelet-derived growth factor receptor b (PDGFRb) (Golub et al, 1994). The self-association of T/P mediated by the helix ± loop ± helix (HLH) domain of TEL leads to constitutive activation of the PDGFRb tyrosine kinase and stimulation of PDGFRb-dependent signalling pathways (Carroll et al, 1996;Jousset et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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The oncogenic TEL/PDGFRβ fusion protein induces cell death through JNK/SAPK pathway

et al. 1999

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Section: Vectorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The oncogenic TEL/PDGFRβ fusion protein induces cell death through JNK/SAPK pathway

et al. 1999

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“…The TEL gene, located at chromosomal band 12p13, was ®rst isolated during the study of the t(5;12)(q33;p13) translocation (Golub et al, 1994). Since then, it has been shown to be involved in a variety of translocations seen in human hematopoietic malignancies Golub et al, 1996b).…”

Section: Introductionmentioning

confidence: 99%

“…Most of them result in transcription of fusion genes between TEL and a partner gene on the other chromosome. Strikingly, partner genes encode di erent sorts of proteins, such as transcription factors (AML1, MN1, EVI-1) (Buijs et al, 1995;Golub et al, 1995;Peeters et al, 1997a;Romana et al, 1995a) or protein kinases (PDGFRb, ABL, JAK2), (Golub et al, 1994;Lacronique et al, 1997;Papadopoulos et al, 1995;Peeters et al, 1997b). In addition, the breakpoints of the di erent translocations within TEL are not clustered, further underscoring the di erential involvement of TEL in the leukemogenic process.…”

Section: Introductionmentioning

confidence: 99%

Analysis of TEL proteins in human leukemias

et al. 1998

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Chromosomal translocations involving the human 12p13 band frequently a ect the TEL gene, usually resulting in gene fusion between TEL and genes encoding proteins of various types. The most frequent 12p13 translocation is the t(12;21)(p13;q22), which recombines TEL with the AML1 gene on chromosome 21 and is frequently associated with deletion of the untranslocated TEL allele. Using antisera against di erent parts of TEL and against the AML1 proteins, we undertook Western blot and immuno¯uorescence analyses of leukemic samples with and without 12p13 abnormalities. In t(12;21) samples, TEL-AML1 was detected as several protein species in the nuclei, whereas the AML1-TEL protein, was inconsistently expressed. AML1 was found to be expressed but no normal TEL proteins were detected. A survey of the TEL proteins in a panel of human leukemic samples without t(12;21) revealed a variation in the ratio of TEL protein isoforms. We also analysed a leukemic cell line bearing a t(12;22)(p13;q11) that was found to a ect the 5' untranslated (UT) region of TEL and to be associated with inactivation of the untranslocated TEL allele. No MN1-TEL fusion could be detected upon RT ± PCR analysis, in contrast to the previously investigated t(12;22). Strikingly, extremely low levels of apparently normal TEL proteins, expressed from the translocated allele, were detected by Western blot analysis. These results suggest that the level of TEL expression can be important for leukemogenesis.

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“…46 TEL-PDGFR␤ can confer cytokine independent growth to Ba/F3 cells. 47 Imatinib mesylate inhibits the kinase PDGFR␤ and is effective therapy in patients with this translocation.…”

Section: Constitutively Active Kinases As Targets Of Therapymentioning

confidence: 99%