Transformation of human CD34+ hematopoietic progenitor cells with DEK-NUP214 induces AML in an immunocompromised mouse model.

Abstract:

:Acute myeloid leukemia (AML) is a heterogeneous disease comprising a large number of subtypes defined by specific chromosome abnormalities. One such subtype carries the t(6;9)(p22;q34) chromosome rearrangement, which leads to expression of the DEK-NUP214 chimeric gene, and has a particularly poor outcome. To provide a better understanding of the molecular etiology of these relatively rare individual AML variants, it is necessary to generate in vivo models, which can also serve as a means to evaluate targeted therapies based on their specific genetic abnormalities. Here, we describe the development of a human cell AML, generated in CD34+ human hematopoietic progenitor cells xenografted into immunocompromised mice that express human myeloid cell growth factors. Within 6 months, these mice develop a human cell AML with phenotypic characteristics of the primary t(6;9) disease and a CD45+CD13+CD34+CD38+ immunophenotype. Gene expression studies show that members of the HOX family of genes (HOXA9, 10, B3, B4 and PBX3) are highly upregulated in the AML from this mouse model as well as from primary human t(6;9) AML. Gene expression analysis also identified several other significantly disregulated pathways involving KRAS, BRCA1 and ALK, for example. This is the first report of a humanized model of the DEK-NUP214 disease and provides a means to study the development and treatment of this particular subtype of AML.

journal_name

Oncogene

journal_title

Oncogene

authors

Qin H,Malek S,Cowell JK,Ren M

doi

10.1038/onc.2016.118

subject

Has Abstract

pub_date

2016-10-27 00:00:00

pages

5686-5691

issue

43

eissn

0950-9232

issn

1476-5594

pii

onc2016118

journal_volume

35

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin.

    abstract::It is well known that intracellular antioxidant glutathione (GSH) plays major roles in the maintenance of redox status and defense of oxidative stress. Ras, a small GTP-binding protein, may send growth-stimulating message to the nucleus through downstream Rac oncoprotein and superoxide (O(2*-)). These findings led us ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206289

    authors: Chuang JI,Chang TY,Liu HS

    更新日期:2003-03-06 00:00:00

  • Transcriptional and post-transcriptional induction of the TGFalpha gene in transformed rat liver epithelial cells.

    abstract::Although TGFalpha mRNA and protein are frequently elevated in neoplastic cells, neither the level at which deregulation occurs nor the mechanism(s) responsible have been well characterized. As a first step, we examined the induction of TGFalpha mRNA in two series of clonally-derived rat liver epithelial cell lines tha...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Berkowitz EA,Hissong MA,Lee DC

    更新日期:1996-05-02 00:00:00

  • ZNF185, an actin-cytoskeleton-associated growth inhibitory LIM protein in prostate cancer.

    abstract::We have recently identified ZNF185 as a gene that is downregulated in prostate cancer (PCa), in part via epigenetic alteration, and maybe associated with disease progression. In this study, we cloned the ZNF185 cDNA from normal human prostate tissues and investigated its biological function. We show that ZNF185 is a n...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209769

    authors: Zhang JS,Gong A,Young CY

    更新日期:2007-01-04 00:00:00

  • Formation of PML/RAR alpha high molecular weight nuclear complexes through the PML coiled-coil region is essential for the PML/RAR alpha-mediated retinoic acid response.

    abstract::Retinoic Acid (RA) treatment induces disease remission of Acute Promyelocytic Leukaemia (APL) patients by triggering terminal differentiation of neoplastic cells. RA-sensitivity in APL is mediated by its oncogenic protein, which results from the recombination of the PML and the RA receptor alpha (RAR alpha) genes (PML...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203029

    authors: Grignani F,Gelmetti V,Fanelli M,Rogaia D,De Matteis S,Ferrara FF,Bonci D,Grignani F,Nervi C,Pelicci PG

    更新日期:1999-11-04 00:00:00

  • PEA3, Oct 1 and Oct 2 positively regulate the human ETS1 promoter.

    abstract::The promoter of the human ETS1 gene contains binding site motifs for transcription factors Sp1, Ap1, Ap2, ETS, PEA3 and Oct. It has been shown previously that Ap1, Ap2, and ETS are positive regulators for the transcription of the ETS1 gene and that the ETS1 gene is autoregulated. In addition, two regions on the ETS1 p...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Chen JH,Wright CD

    更新日期:1993-12-01 00:00:00

  • Transformation by v-Myb.

    abstract::The v-myb oncogene of the avian myeloblastosis virus (AMV) is unique among known oncogenes in that it causes only acute leukemia in animals and transforms only hematopoietic cells in culture. AMV was discovered in the 1930s as a virus that caused a disease in chickens that is similar to acute myelogenous leukemia in h...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1202745

    authors: Lipsick JS,Wang DM

    更新日期:1999-05-13 00:00:00

  • SALL4, a novel marker for human gastric carcinogenesis and metastasis.

    abstract::SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.495

    authors: Zhang L,Xu Z,Xu X,Zhang B,Wu H,Wang M,Zhang X,Yang T,Cai J,Yan Y,Mao F,Zhu W,Shao Q,Qian H,Xu W

    更新日期:2014-11-27 00:00:00

  • Molecular mechanisms underlying interferon-alpha-induced G0/G1 arrest: CKI-mediated regulation of G1 Cdk-complexes and activation of pocket proteins.

    abstract::One prominent effect of IFNs is their cell growth-inhibitory activity. The mechanism behind this inhibition of proliferation is still not fully understood. In this study, the effect of IFN-alpha treatment on cell cycle progression has been analysed in three lymphoid cell lines, Daudi, U-266 and H9. Examination of the ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202609

    authors: Sangfelt O,Erickson S,Castro J,Heiden T,Gustafsson A,Einhorn S,Grandér D

    更新日期:1999-05-06 00:00:00

  • Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth.

    abstract::AP-1 transcription factors play a critical role in signal transduction pathways in many cells. We have investigated the role of AP-1 in controlling proliferative signals in breast cells, and have previously shown that AP-1 complexes are activated by peptide and steroid growth factors in both normal and malignant breas...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205883

    authors: Liu Y,Ludes-Meyers J,Zhang Y,Munoz-Medellin D,Kim HT,Lu C,Ge G,Schiff R,Hilsenbeck SG,Osborne CK,Brown PH

    更新日期:2002-10-31 00:00:00

  • Defective cleavage of membrane bound TGFalpha leads to enhanced activation of the EGF receptor in malignant cells.

    abstract::Transforming growth factor alpha (TGFalpha) is widely expressed in malignant as well as normal cells and is involved in regulating cell growth and differentiation. Although processing of TGFalpha has been extensively studied in normal cells, there is little information regarding TGFalpha cleavage in malignant cells. T...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203513

    authors: Yang H,Jiang D,Li W,Liang J,Gentry LE,Brattain MG

    更新日期:2000-04-06 00:00:00

  • Differential modulation of Myb family genes by Ets-2.

    abstract::The myb family of genes encodes highly homologous nuclear transcription factors that play distinct roles in the development of breast, germ cells and hematoid organs. While the mechanisms associated with the regulation of these genes remain unknown, the transactivation of c-Myb was previously shown to be upregulated b...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207537

    authors: Kang AD,Park G,Kim YH,Oh IH

    更新日期:2004-05-20 00:00:00

  • Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice.

    abstract::The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tis...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203366

    authors: Bouvard V,Zaitchouk T,Vacher M,Duthu A,Canivet M,Choisy-Rossi C,Nieruchalski M,May E

    更新日期:2000-02-03 00:00:00

  • Somatic mutations in the human homologue of Drosophila patched in primitive neuroectodermal tumours.

    abstract::The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple developmental defects and cancer susceptibility, in particular to basal cell carcinomas (BCCs). Medulloblastomas, primitive neuroectodermal tumours (PNETs) arising in childhood, occur in about 3-5% of NBCCS pa...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201340

    authors: Vorechovský I,Tingby O,Hartman M,Strömberg B,Nister M,Collins VP,Toftgård R

    更新日期:1997-07-17 00:00:00

  • The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression.

    abstract::The transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01477-8

    authors: Jessen C,Kreß JKC,Baluapuri A,Hufnagel A,Schmitz W,Kneitz S,Roth S,Marquardt A,Appenzeller S,Ade CP,Glutsch V,Wobser M,Friedmann-Angeli JP,Mosteo L,Goding CR,Schilling B,Geissinger E,Wolf E,Meierjohann S

    更新日期:2020-10-01 00:00:00

  • Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis.

    abstract::Ras oncogenes (Hras, Kras and Nras) are important drivers of carcinogenesis. However, tumors with Ras mutations often show loss of the corresponding wild-type (WT) allele, suggesting that proto-oncogenic forms of Ras can function as a suppressor of carcinogenesis. In vitro studies also suggest that WT Ras proteins can...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.404

    authors: To MD,Rosario RD,Westcott PM,Banta KL,Balmain A

    更新日期:2013-08-22 00:00:00

  • Inactivation of ELF/TGF-beta signaling in human gastrointestinal cancer.

    abstract::TGF-beta/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. ELF, a beta-spectrin, plays a key role in the transmission of TGF-beta-mediated transcriptional response through Smads. ELF was originally identified as a key protein involved in endodermal stem/progenito...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208946

    authors: Katuri V,Tang Y,Marshall B,Rashid A,Jogunoori W,Volpe EA,Sidawy AN,Evans S,Blay J,Gallicano GI,Premkumar Reddy E,Mishra L,Mishra B

    更新日期:2005-12-01 00:00:00

  • Nuclear import of LASP-1 is regulated by phosphorylation and dynamic protein-protein interactions.

    abstract::LASP-1 is a multidomain protein predominantly localized at focal contacts, where it regulates cytoskeleton dynamics and cell migration. However, in different tumor entities, a nuclear LASP-1 accumulation is observed, thought to have an important role in cancer progression. Until now, the molecular mechanisms that cont...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.216

    authors: Mihlan S,Reiß C,Thalheimer P,Herterich S,Gaetzner S,Kremerskothen J,Pavenstädt HJ,Lewandrowski U,Sickmann A,Butt E

    更新日期:2013-04-18 00:00:00

  • Screening for mutations in exon 11 of the BRCA1 gene in 70 Italian breast and ovarian cancer patients by protein truncation test.

    abstract::The most common mutations in the familial breast and ovarian cancer susceptibility gene BRCA1 are frameshift and nonsense mutations, which lead to the synthesis of truncated proteins. On this ground, we have analysed BRCA1 exon 11, which includes about 61% of coding region, in germline DNA from 70 Italian breast and/o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: De Benedetti VM,Radice P,Mondini P,Spatti G,Conti A,Illeni MT,Caligo MA,Cipollini G,Bevilaqua G,Pilotti S,Pierotti MA

    更新日期:1996-09-19 00:00:00

  • MacroH2A1.2 inhibits prostate cancer-induced osteoclastogenesis through cooperation with HP1α and H1.2.

    abstract::Osteoclasts are multinuclear bone-resorbing cells that differentiate from hematopoietic precursor cells. Prostate cancer cells frequently spread to bone and secrete soluble signaling factors to accelerate osteoclast differentiation and bone resorption. However, processes and mechanisms that govern the expression of os...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0356-3

    authors: Kim JM,Shin Y,Lee S,Kim MY,Punj V,Shin HI,Kim K,Koh JM,Jeong D,An W

    更新日期:2018-10-01 00:00:00

  • A novel mechanism for the control of translation of specific mRNAs by tumor suppressor protein Pdcd4: inhibition of translation elongation.

    abstract::The tumor suppressor gene Pdcd4 (programmed cell death gene 4) has drawn considerable attention because its downregulation is involved in the development of several types of cancer. Because Pdcd4 interacts with the translation initiation factor eIF4A and inhibits its helicase activity, Pdcd4 has been implicated in the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.83

    authors: Biyanee A,Ohnheiser J,Singh P,Klempnauer KH

    更新日期:2015-03-12 00:00:00

  • Characterization of ret proto-oncogene mRNAs encoding two isoforms of the protein product in a human neuroblastoma cell line.

    abstract::The ret proto-oncogene expresses four major mRNA species of different lengths in human malignant cell lines and rat tissues. We isolated ret proto-oncogene cDNA clones from a cDNA library of a human neuroblastoma line, Nagai, which over-expressed these mRNAs. Four cDNA clones differing from each other in their 3' port...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Tahira T,Ishizaka Y,Itoh F,Sugimura T,Nagao M

    更新日期:1990-01-01 00:00:00

  • Involvement of Bcl-X(L) deamidation in E1A-mediated cisplatin sensitization of ovarian cancer cells.

    abstract::The adenovirus E1A protein has been shown to be involved in the potentiation of apoptosis induced by chemotherapeutic agents, yet the molecular events of E1A-mediated apoptosis are not very clear. A recent report has suggested that deamidation of the Bcl-X(L) protein inhibits its antiapoptotic ability and leads to apo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209294

    authors: Chang CY,Lin YM,Lee WP,Hsu HH,Chen EI

    更新日期:2006-04-27 00:00:00

  • C-myb proto-oncogene: evidence for intermolecular recombination of coding sequences.

    abstract::We have characterized a novel chicken c-myb exon whose sequences are specifically expressed in thymic cells. In situ hybridization experiments indicate that this thymus-specific coding exon is localized on a small chromosome, distinct from the large acrocentric chromosome 3 on which we recently mapped the bulk of 15 e...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Vellard M,Soret J,Viegas-Pequignot E,Galibert F,Nguyen VC,Dutrillaux B,Perbal B

    更新日期:1991-04-01 00:00:00

  • Roles of tyrosine residues 845, 892 and 922 in constitutive activation of murine FLT3 kinase domain mutant.

    abstract::FLT3 tyrosine kinase domain (TKD) mutations are detected in approximately 7% of acute myeloid leukemia patients, and suggested to correlate with poor prognosis and confer resistance to FLT3 inhibitors. To explore activation mechanism of FLT3 TKD mutation, we analysed critical tyrosine residues for the constitutive act...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208957

    authors: Ishiko J,Mizuki M,Matsumura I,Shibayama H,Sugahara H,Scholz G,Serve H,Kanakura Y

    更新日期:2005-12-08 00:00:00

  • Alternative splicing in cancer: implications for biology and therapy.

    abstract::Alternative splicing has critical roles in normal development and can promote growth and survival in cancer. Aberrant splicing, the production of noncanonical and cancer-specific mRNA transcripts, can lead to loss-of-function in tumor suppressors or activation of oncogenes and cancer pathways. Emerging data suggest th...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2013.570

    authors: Chen J,Weiss WA

    更新日期:2015-01-02 00:00:00

  • Sorting out functions of sirtuins in cancer.

    abstract::The sirtuins (SIRT 1-7) comprise a family of NAD⁺-dependent protein-modifying enzymes with activities in lysine deacetylation, adenosinediphospho(ADP)-ribosylation, and/or deacylation. These enzymes are involved in the cell's stress response systems and in regulating gene expression, DNA damage repair, metabolism and ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2013.120

    authors: Roth M,Chen WY

    更新日期:2014-03-27 00:00:00

  • PML protein isoforms and the RBCC/TRIM motif.

    abstract::PML is a component of a multiprotein complex, termed nuclear bodies, and the PML protein was originally discovered in patients suffering from acute promyelocytic leukaemia (APL). APL is associated with a reciprocal chromosomal translocation of chromosomes 15 and 17, which results in a fusion protein comprising PML and...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1204765

    authors: Jensen K,Shiels C,Freemont PS

    更新日期:2001-10-29 00:00:00

  • Oligomerization of p53 is necessary to inhibit its transcriptional transactivation property at high protein concentration.

    abstract::We have previously shown that transactivation by tumor suppressor protein p53 can be inhibited in vivo at elevated protein concentrations. In this study we characterize the structural requirements of this function. We show that oligomerization domain of p53 is involved in loss of transactivation at high protein concen...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201749

    authors: Kristjuhan A,Jaks V,Rimm I,Tooming T,Maimets T

    更新日期:1998-05-07 00:00:00

  • Modulation of p53 dependent gene expression and cell death through thioredoxin-thioredoxin reductase by the Interferon-Retinoid combination.

    abstract::We have shown earlier that the IFN-beta and all-trans retinoic acid (RA) combination, but not the single agents, induces death in several tumor cell lines. Employing a genetic technique we have identified several Genes associated with Retinoid-IFN induced Mortality (GRIM). One of the GRIMs was human thioredoxin reduct...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204585

    authors: Hu J,Ma X,Lindner DJ,Karra S,Hofmann ER,Reddy SP,Kalvakolanu DV

    更新日期:2001-07-12 00:00:00

  • A Herpes saimiri oncogene causing peripheral T-cell lymphoma in transgenic mice.

    abstract::Herpesvirus saimiri is an oncogenic virus causing rapid T-cell lymphomas in New World primates and rabbits. Deletion analysis of one strain of H saimiri has indicated an open reading frame, StpA, necessary for oncongenicity in monkeys. We have investigated the function of StpA in tumor induction by the generation of t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Kretschmer C,Murphy C,Biesinger B,Beckers J,Fickenscher H,Kirchner T,Fleckenstein B,Rüther U

    更新日期:1996-04-18 00:00:00