Cooperation of Myb and Myc proteins in T cell lymphomagenesis

Davies, Joanna P.; Badiani, Pratipa; Weston, Kathleen

doi:10.1038/sj.onc.1202956

Cited by 22 publications

(17 citation statements)

References 26 publications

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“…Further evidence that Myb and Myc may act in concert to promote the development of T-cell lymphoma came from a study of MMLV accelerated tumors of CD2-vMyb mice, in which c-myc was identified as a target for proviral insertional activation (10). To confirm that these genes act in synergy, we examined the effect of combining the CD2-vMyb and CD2-MYC-ER transgenes on tumor development.…”

Section: Resultsmentioning

confidence: 99%

Long-Range Effects of Retroviral Insertion on c -myb : Overexpression May Be Obscured by Silencing during Tumor Growth In Vitro

Hanlon

Barr

Blyth

et al. 2003

J Virol

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The c-myb oncogene is a frequent target for retroviral activation in hemopoietic tumors of avian and mammalian species. While insertions can target the gene directly, numerous clusters of retroviral insertion sites have been identified which map close to c-myb and outside the transcription unit in T-lymphomas (Ahi-1, fit-1, and Mis-2) and monocytic and myeloid leukemias (Mml1, Mml2, Mml3, and Epi-1). Previous analyses showed no consistent effect of these insertions on c-myb expression, raising the possibility that other nearby genes were the true targets. In contrast, our analysis of four cell lines established from lymphomas bearing insertions at fit-1 (fti-1) (feline leukemia virus) and Ahi-1 (Moloney murine leukemia virus) shows that these display higher expression levels of c-myb RNA and protein compared to a panel of phenotypically similar cell lines lacking such insertions. An interesting feature of the cell lines with long-range c-myb insertions was that each also carried an activated Myc allele. The potential for oncogenic synergy between Myb and Myc in T-cell lymphoma was confirmed in transgenic mice overexpressing alleles of both genes in the T-cell compartment, lending further credence to the case for c-myb as the major target for long-range activation. In contrast, mapping and analysis of c-myb neighboring genes (HBS1 and FLJ20069) showed that the expression of these genes did not correlate well with the presence of proviral insertions. A possible explanation for the paradoxical behavior of c-myb was provided by one of the murine T-lymphoma lines bearing an insertion at Ahi-1 (p/m16i) that reproducibly down-regulated c-myb RNA and protein to very low levels or undetectable levels on prolonged culture. Our observations implicate c-myb as a key target of upstream and downstream retroviral insertions. However, overexpression may become dispensable during outgrowth in vitro, and perhaps during tumor progression in vivo, providing a potential rationale for the previously observed discordance between retroviral insertion and c-myb expression levels.

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Section: Resultsmentioning

confidence: 99%

Long-Range Effects of Retroviral Insertion on c -myb : Overexpression May Be Obscured by Silencing during Tumor Growth In Vitro

Hanlon

Barr

Blyth

et al. 2003

J Virol

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“…The c-Myb proto-oncogene, cellular homolog of the avian myeloblastosis virus (AMV) and avian leukemia virus (E26) transforming genes (Klempnauer et al, 1984), is predominantly expressed in hematopoietic tissues and plays a role in tumorigenesis (Ness, 1999;Weston, 1999;Davies et al, 1999). c-Myb is a transcription factor that transactivates several cellular promoters (reviewed in Thompson and Ramsay, 1995).…”

Section: Introductionmentioning

confidence: 99%

HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300

et al. 2000

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“…In Eu-v-abl mice, c-myc and Nmyc were tagged as oncogenic partners (Haupt et al, 1993). In addition, myb, pim-1, bmi-1/bla-1, pal-1, and raf-1 have been shown to cooperate with c-myc (Davies et al, 1999;Evan and Littlewood, 1993;Packham and Cleveland, 1995), where some of these genes, namely, pim1, raf and abl, exhibit anti-apoptotic activity.…”

Section: Myc and Tumorigenesismentioning

confidence: 99%

The proto-oncogene c-myc in hematopoietic development and leukemogenesis

et al. 2002

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The proto-oncogene c-myc has been shown to play a pivotal role in cell cycle regulation, metabolism, apoptosis, dierentiation, cell adhesion, and tumorigenesis, and participates in regulating hematopoietic homeostasis. It is a transcription regulator that is part of an extensive network of interacting factors. Most probably, dierent biological responses are elicited by dierent overlapping subsets of c-Myc target genes, both induced and suppressed. Results obtained from studies employing mouse models are consistent with the need for at least one, and possibly two, mutations in addition to deregulated c-myc for malignant tumor formation. Repression of c-myc is required for terminal dierentiation of many cell types, including hematopoietic cells. It has been shown that deregulated expression of c-myc in both M1 myeloid leukemic cells and normal myeloid cells derived from murine bone marrow, not only blocked terminal dierentiation and its associated growth arrest, but also induced apoptosis, which is dependent on the Fas/CD95 pathway. There is evidence to suggest that the CD95/Fas death receptor pathway is an integral part of the apoptotic response associated with the end of the normal terminal myeloid dierentiation program, and that deregulated c-myc expression can activate this signaling pathway prematurely. The ability of egr-1 to promote terminal myeloid dierentiation when coexpressed with c-myc, and of c-fos to partially abrogate the block imparted by deregulated c-myc on myeloid dierentiation, make these two genes candidate tumor suppressors. Several dierent transcription factors have been implicated in the down-regulation of c-myc expression during dierentiation, including C/EBPa, CTCF, BLIMP-1, and RFX1. Alterations in the expression and/or function of these transcription factors, or of the c-Myc and Max interacting proteins, such as MM-1 and Mxi1, can in¯uence the neoplastic process. Understanding how c-Myc controls cellular phenotypes, including the leukemic phenotype, should provide novel tools for designing drugs to promote dierentiation and/ or apoptosis of leukemic cells.

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Cooperation of Myb and Myc proteins in T cell lymphomagenesis

Cited by 22 publications

References 26 publications

Long-Range Effects of Retroviral Insertion on c -myb : Overexpression May Be Obscured by Silencing during Tumor Growth In Vitro

Long-Range Effects of Retroviral Insertion on c -myb : Overexpression May Be Obscured by Silencing during Tumor Growth In Vitro

HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300

The proto-oncogene c-myc in hematopoietic development and leukemogenesis

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