Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice

Shing, D.; Trubia, Maurizio; Marchesi, Francesco; Radælli, Enrico; Belloni, Elena; Tapinassi, Cinzia; Scanziani, Eugenio; Mecucci, Cristina; Crescenzi, Barbara; Lahortiga, Idoya; Odero, Marı́a D.; Zardo, Giuseppe; Gruszka-Westwood, Alicja M.; Minucci, Saverio; Fiore, Pier Paolo Di; Pelicci, Pier Giuseppe

doi:10.1172/jci32390

Cited by 55 publications

(81 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CALGB (Cancer and Leukemia Group B) study showed significantly prolonged median time to progression to leukaemia and/or death, whereas AZA 001 trial showed a prolonged overall survival (OS) compared with conventional care regimens. [1][2][3] Recently, it has been reported that abnormal karyotype independently predicted lower response rates to azacitidine and that intermediate-and poor-risk cytogenetics independently predicted poorer OS. 4 Inversion of chromosome 3 (inv(3) (q21;q26)), with EVI-1 (ecotropic viral integration site 1) transcriptional activation, is relatively common in myeloid malignancies and was reported in acute myeloid leukaemia, chronic myeloid leukaemia in blast crisis and myelodysplastic syndromes (MDS).…”

Section: Conflict Of Interestmentioning

confidence: 99%

“…1 Transgenic expression of the generated aberrant transcripts and corresponding fusion proteins often induces leukemia in mice, suggesting a role in disease onset. 2 The MYB gene, on human chromosome 6, corresponds to a 75-kDa transcription factor exerting a physiological function in the hematopoietic system (reviewed in Ramsay and Gonda 3 ). GATA1, a nuclear protein with an essential role in hematopoiesis, is coded by a gene located on the human X chromosome (reviewed in Shimizu et al 4 ).…”

mentioning

confidence: 99%

See 1 more Smart Citation

In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

et al. 2011

View full text Add to dashboard Cite

Section: Conflict Of Interestmentioning

confidence: 99%

mentioning

confidence: 99%

In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

et al. 2011

View full text Add to dashboard Cite

“…More than half of these immortalized lines had activating proviral insertional mutations in two well-known human myeloid leukemia oncogenes important for hematopoietic stem cell self-renewal, Evi1 and Prdm16 (35,36). These immortalized immature myeloid cells were not tumorigenic in transplanted hosts, however, probably because the retrovirus used in these experiments was replication-defective and could not induce the additional rounds of insertional mutations required for tumor development in transplanted mice.…”

Section: Discussionmentioning

confidence: 96%

Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells

Koso

Takeda

Yew

et al. 2012

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

View full text Add to dashboard Cite

Neural stem cells (NSCs) are considered to be the cell of origin of glioblastoma multiforme (GBM). However, the genetic alterations that transform NSCs into glioma-initiating cells remain elusive. Using a unique transposon mutagenesis strategy that mutagenizes NSCs in culture, followed by additional rounds of mutagenesis to generate tumors in vivo, we have identified genes and signaling pathways that can transform NSCs into glioma-initiating cells. Mobilization of Sleeping Beauty transposons in NSCs induced the immortalization of astroglial-like cells, which were then able to generate tumors with characteristics of the mesenchymal subtype of GBM on transplantation, consistent with a potential astroglial origin for mesenchymal GBM. Sequence analysis of transposon insertion sites from tumors and immortalized cells identified more than 200 frequently mutated genes, including human GBM-associated genes, such as Met and Nf1, and made it possible to discriminate between genes that function during astroglial immortalization vs. later stages of tumor development. We also functionally validated five GBM candidate genes using a previously undescribed high-throughput method. Finally, we show that even clonally related tumors derived from the same immortalized line have acquired distinct combinations of genetic alterations during tumor development, suggesting that tumor formation in this model system involves competition among genetically variant cells, which is similar to the Darwinian evolutionary processes now thought to generate many human cancers. This mutagenesis strategy is faster and simpler than conventional transposon screens and can potentially be applied to any tissue stem/progenitor cells that can be grown and differentiated in vitro.

show abstract

“…In addition, the expression patterns implied that the PRDM16 gene has additional functions besides its roles on brown fat tissues. For instance, the up-regulation of PRDM16 could initiate a leukemogenic cascade (Shing et al, 2007;Modlich et al, 2008), and the copy number of PRDM16 molecules of patients with osteosarcoma was higher than that of the normal (Man et al, 2004).…”

mentioning

confidence: 99%

Identification of gene variation within porcine PRDM16 gene and its association with fat and loin muscle area

Niu¹,

Zhao²,

Fan³

2010

SA J. An. Sci.

View full text Add to dashboard Cite

The PR domain containing the 16 (PRDM16) gene, also known as the MDS1/EVI1-like gene (MEL1), may act as a bidirectional switch between brown fat and skeletal muscle in mice. The molecular characteristics and possible biological function of porcine PRDM16 gene have been less reported. In this study, the mRNA expression profile, linkage mapping and association analyses of the PRDM16 gene were carried out in the pig. The PRDM16 mRNA was expressed widely in various tissues including fat and the longissimus dorsi muscle. One SNP c.-3284+171C>T in intron 14 was identified and that made the PRDM16 gene being assigned between SWR1130 and SW122 on SSC6. The different genotypes of c.-3284+171C>T were significantly associated with backfat and loin muscle area in the ISU Berkshire × Yorkshire pig resource family, but such associations were not verified in another pig population. The discovery of additional mutations and association studies are warranted before the PRDM16 gene can be recommended for marker assisted selection in the pig. _______________________________________________________________________________________

show abstract

Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice

Cited by 55 publications

References 45 publications

In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells

Identification of gene variation within porcine PRDM16 gene and its association with fat and loin muscle area

Contact Info

Product

Resources

About