PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice.

Abstract:

:PAX5 is a well-known haploinsufficient tumor suppressor gene in human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is involved in various chromosomal translocations that fuse a part of PAX5 with other partners. However, the role of PAX5 fusion proteins in B-ALL initiation and transformation is ill-known. We previously reported a new recurrent t(7;9)(q11;p13) chromosomal translocation in human B-ALL that juxtaposed PAX5 to the coding sequence of elastin (ELN). To study the function of the resulting PAX5-ELN fusion protein in B-ALL development, we generated a knockin mouse model in which the PAX5-ELN transgene is expressed specifically in B cells. PAX5-ELN-expressing mice efficiently developed B-ALL with an incidence of 80%. Leukemic transformation was associated with recurrent secondary mutations on Ptpn11, Kras, Pax5, and Jak3 genes affecting key signaling pathways required for cell proliferation. Our functional studies demonstrate that PAX5-ELN affected B-cell development in vitro and in vivo featuring an aberrant expansion of the pro-B cell compartment at the preleukemic stage. Finally, our molecular and computational approaches identified PAX5-ELN-regulated gene candidates that establish the molecular bases of the preleukemic state to drive B-ALL initiation. Hence, our study provides a new in vivo model of human B-ALL and strongly implicates PAX5 fusion proteins as potent oncoproteins in leukemia development.

authors

Jamrog L,Chemin G,Fregona V,Coster L,Pasquet M,Oudinet C,Rouquié N,Prade N,Lagarde S,Cresson C,Hébrard S,Nguyen Huu NS,Bousquet M,Quelen C,Brousset P,Mancini SJC,Delabesse E,Khamlichi AA,Gerby B,Broccardo C

doi

10.1073/pnas.1721678115

subject

Has Abstract

pub_date

2018-10-09 00:00:00

pages

10357-10362

issue

41

eissn

0027-8424

issn

1091-6490

pii

1721678115

journal_volume

115

pub_type

杂志文章
  • Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel.

    abstract::The ecology of microbes in the gut has been shown to play important roles in the health of the host. To better understand microbial growth and population dynamics in the proximal colon, the primary region of bacterial growth in the gut, we built and applied a fluidic channel that we call the "minigut." This is a chann...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1601306113

    authors: Cremer J,Segota I,Yang CY,Arnoldini M,Sauls JT,Zhang Z,Gutierrez E,Groisman A,Hwa T

    更新日期:2016-10-11 00:00:00

  • Enzymatic oligomerization of bacteriophage P22 DNA and of linear Simian virus 40 DNA.

    abstract::Linear double-stranded molecules of the circularly permuted and terminally redundant DNA of Salmonella bacteriophage P22 have been converted to oligomeric products in the presence of polynucleotide ligase coded for by the coliphage T4. The reaction has been monitored by sucrose density-gradient centrifugation and elec...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.11.3389

    authors: Sgaramella V

    更新日期:1972-11-01 00:00:00

  • Galaxy clustering on large scales.

    abstract::I describe some recent observations of large-scale structure in the galaxy distribution. The best constraints come from two-dimensional galaxy surveys and studies of angular correlation functions. Results from galaxy redshift surveys are much less precise but are consistent with the angular correlations, provided the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.11.4859

    authors: Efstathiou G

    更新日期:1993-06-01 00:00:00

  • Transient HIV-1 Gag-protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations.

    abstract::Cleavage of the group-specific antigen (Gag) polyprotein by HIV-1 protease represents the critical first step in the conversion of immature noninfectious viral particles to mature infectious virions. Selective pressure exerted by HIV-1 protease inhibitors, a mainstay of current anti-HIV-1 therapies, results in the acc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1615342113

    authors: Deshmukh L,Louis JM,Ghirlando R,Clore GM

    更新日期:2016-11-01 00:00:00

  • A method for mapping intranuclear protein-DNA interactions and its application to a nuclease hypersensitive site.

    abstract::We have devised a method for mapping sites on DNA within the nucleus that are protected against nuclease attack by interaction with bound protein or other factors. This "footprinting" method uses an end-labeled sequence-specific DNA probe, which is annealed to the DNA from nuclear digests under carefully controlled co...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.8.2296

    authors: Jackson PD,Felsenfeld G

    更新日期:1985-04-01 00:00:00

  • Methods for causal inference from gene perturbation experiments and validation.

    abstract::Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1510493113

    authors: Meinshausen N,Hauser A,Mooij JM,Peters J,Versteeg P,Bühlmann P

    更新日期:2016-07-05 00:00:00

  • Gating charge interactions with the S1 segment during activation of a Na+ channel voltage sensor.

    abstract::Voltage-gated Na(+) channels initiate action potentials during electrical signaling in excitable cells. Opening and closing of the pore of voltage-gated ion channels are mechanically linked to voltage-driven outward movement of the positively charged S4 transmembrane segment in their voltage sensors. Disulfide locking...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1116449108

    authors: DeCaen PG,Yarov-Yarovoy V,Scheuer T,Catterall WA

    更新日期:2011-11-15 00:00:00

  • Structure, function, and self-assembly of single network gyroid (I4132) photonic crystals in butterfly wing scales.

    abstract::Complex three-dimensional biophotonic nanostructures produce the vivid structural colors of many butterfly wing scales, but their exact nanoscale organization is uncertain. We used small angle X-ray scattering (SAXS) on single scales to characterize the 3D photonic nanostructures of five butterfly species from two fam...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0909616107

    authors: Saranathan V,Osuji CO,Mochrie SG,Noh H,Narayanan S,Sandy A,Dufresne ER,Prum RO

    更新日期:2010-06-29 00:00:00

  • Defective antitermination of rRNA transcription and derepression of rRNA and tRNA synthesis in the nusB5 mutant of Escherichia coli.

    abstract::The nusB5 mutant of Escherichia coli was originally selected for reduced ability to support the antitermination of transcription that is mediated by the gene N product of bacteriophage lambda. By analyzing pulse-labeled RNA with an RNA.DNA filter hybridization technique, we have shown that, in the nusB5 mutant, the ra...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.16.5275

    authors: Sharrock RA,Gourse RL,Nomura M

    更新日期:1985-08-01 00:00:00

  • Differential regulation by multiple promoters of the gene encoding the neuron-restrictive silencer factor.

    abstract::NRSF/REST is a protein that silences transcription of a number of genes that contain a DNA element called the neuron-restrictive silencer element (NRSE). During embryogenesis, REST is expressed ubiquitously in nonneural cells, but is down-regulated during differentiation of neural progenitors into neurons. REST is als...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.050578797

    authors: Koenigsberger C,Chicca JJ 2nd,Amoureux MC,Edelman GM,Jones FS

    更新日期:2000-02-29 00:00:00

  • DNA strand-specific repair of (+-)-3 alpha,4 beta-dihydroxy-1 alpha,2 alpha-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene adducts in the hamster dihydrofolate reductase gene.

    abstract::We evaluated the formation and removal of (+-)-3 alpha,4 beta-dihydroxy-1 alpha,2 alpha-epoxy-1,2,3,4- tetrahydrobenzo[c]phenanthrene (BcPHDE)-DNA adducts in two Chinese hamster ovary (CHO) cell lines. One line of repair-proficient cells (MK42) carries a stable 150-fold amplification of the dihydrofolate reductase (DH...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.24.11925

    authors: Carothers AM,Zhen W,Mucha J,Zhang YJ,Santella RM,Grunberger D,Bohr VA

    更新日期:1992-12-15 00:00:00

  • BiP mutants that are unable to interact with endoplasmic reticulum DnaJ proteins provide insights into interdomain interactions in BiP.

    abstract::The heat shock protein (Hsp)70 family of molecular chaperones interacts with unfolded proteins through a C-terminal substrate-binding domain (SBD) that is controlled by nucleotide binding to the N-terminal domain. The ATPase cycle is regulated by cochaperones, including DnaJ proteins that accelerate ATP hydrolysis to ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0702132105

    authors: Awad W,Estrada I,Shen Y,Hendershot LM

    更新日期:2008-01-29 00:00:00

  • Calibrating the coevolution of Ediacaran life and environment.

    abstract::The rise of animals occurred during an interval of Earth history that witnessed dynamic marine redox conditions, potentially rapid plate motions, and uniquely large perturbations to global biogeochemical cycles. The largest of these perturbations, the Shuram carbon isotope excursion, has been invoked as a driving mech...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2002918117

    authors: Rooney AD,Cantine MD,Bergmann KD,Gómez-Pérez I,Al Baloushi B,Boag TH,Busch JF,Sperling EA,Strauss JV

    更新日期:2020-07-21 00:00:00

  • NTRC-dependent redox balance of 2-Cys peroxiredoxins is needed for optimal function of the photosynthetic apparatus.

    abstract::Thiol-dependent redox regulation allows the rapid adaptation of chloroplast function to unpredictable changes in light intensity. Traditionally, it has been considered that chloroplast redox regulation relies on photosynthetically reduced ferredoxin (Fd), thioredoxins (Trxs), and an Fd-dependent Trx reductase (FTR), t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1706003114

    authors: Pérez-Ruiz JM,Naranjo B,Ojeda V,Guinea M,Cejudo FJ

    更新日期:2017-11-07 00:00:00

  • Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2.

    abstract::Cyclooxygenase (COX)-2, a rate-limiting enzyme of prostaglandin (PG) production, is overexpressed in colorectal adenomas and adenocarcinomas, and its inhibition by nonsteroidal antiinflammatory drugs protects against colorectal cancer. Mechanisms of cancer promotion by COX-2 are not fully understood, but signaling thr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1533221100

    authors: Nishihara H,Kizaka-Kondoh S,Insel PA,Eckmann L

    更新日期:2003-07-22 00:00:00

  • Short telomeres are a risk factor for idiopathic pulmonary fibrosis.

    abstract::Idiopathic interstitial pneumonias (IIPs) have a progressive and often fatal course, and their enigmatic etiology has complicated approaches to effective therapies. Idiopathic pulmonary fibrosis (IPF) is the most common of IIPs and shares with IIPs an increased incidence with age and unexplained scarring in the lung. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0804280105

    authors: Alder JK,Chen JJ,Lancaster L,Danoff S,Su SC,Cogan JD,Vulto I,Xie M,Qi X,Tuder RM,Phillips JA 3rd,Lansdorp PM,Loyd JE,Armanios MY

    更新日期:2008-09-02 00:00:00

  • Targeted knockout of a chemokine-like gene increases anxiety and fear responses.

    abstract::Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these disea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1707663115

    authors: Choi JH,Jeong YM,Kim S,Lee B,Ariyasiri K,Kim HT,Jung SH,Hwang KS,Choi TI,Park CO,Huh WK,Carl M,Rosenfeld JA,Raskin S,Ma A,Gecz J,Kim HG,Kim JS,Shin HC,Park DS,Gerlai R,Jamieson BB,Kim JS,Iremonger KJ,Lee S

    更新日期:2018-01-30 00:00:00

  • Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus.

    abstract::The origins and consequences of a regulatory T cell (Treg) disorder in systemic lupus erythematosus (SLE) are poorly understood. In the (NZBxNZW) F(1) mouse model of lupus, we found that CD4(+)Foxp3(+) Treg failed to maintain a competitive pool size in the peripheral lymphoid organs resulting in a progressive homeosta...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0903158107

    authors: Humrich JY,Morbach H,Undeutsch R,Enghard P,Rosenberger S,Weigert O,Kloke L,Heimann J,Gaber T,Brandenburg S,Scheffold A,Huehn J,Radbruch A,Burmester GR,Riemekasten G

    更新日期:2010-01-05 00:00:00

  • Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer.

    abstract::This article extends our previous quantitative analysis of the relationship between the dynamics of the primary structure of DNA and mutagenesis associated with single-strand lesions to an analysis of the production and processing of endogenous double-strand breaks (EDSBs) and to their implications for oncogenesis. We...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2135498100

    authors: Vilenchik MM,Knudson AG

    更新日期:2003-10-28 00:00:00

  • Functional mapping of disease susceptibility loci using cell biology.

    abstract::In most genome-wide linkage studies, implication of a causative disease gene often requires years of expanding the study to more families and finer mapping of the initially described region. Even after such efforts, unobtainable sample sizes can be required to make statistically meaningful conclusions about a single g...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0510521103

    authors: Antinozzi PA,Garcia-Diaz A,Hu C,Rothman JE

    更新日期:2006-03-07 00:00:00

  • Structure of the Leanyer orthobunyavirus nucleoprotein-RNA complex reveals unique architecture for RNA encapsidation.

    abstract::Negative-stranded RNA viruses cover their genome with nucleoprotein (N) to protect it from the human innate immune system. Abrogation of the function of N offers a unique opportunity to combat the spread of the viruses. Here, we describe a unique fold of N from Leanyer virus (LEAV, Orthobunyavirus genus, Bunyaviridae ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1300035110

    authors: Niu F,Shaw N,Wang YE,Jiao L,Ding W,Li X,Zhu P,Upur H,Ouyang S,Cheng G,Liu ZJ

    更新日期:2013-05-28 00:00:00

  • Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse.

    abstract::Species- and strain-specific spontaneously occurring tumors have been observed in rodents maintained under normal laboratory conditions. Elucidation of the molecular mechanisms associated with the development of these spontaneous tumors may provide a better understanding of tumor development associated with exposure t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.1.33

    authors: Reynolds SH,Stowers SJ,Maronpot RR,Anderson MW,Aaronson SA

    更新日期:1986-01-01 00:00:00

  • Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation.

    abstract::MST1, mammalian STE20-like kinase 1, is a serine/threonine kinase that is cleaved and activated by caspases during apoptosis. MST1 is capable of inducing apoptotic morphological changes such as chromatin condensation upon overexpression. In this study, we show that MST1 contains two functional nuclear export signals (...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.181161698

    authors: Ura S,Masuyama N,Graves JD,Gotoh Y

    更新日期:2001-08-28 00:00:00

  • Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells.

    abstract::Arsenic has played a key medicinal role against a variety of ailments for several millennia, but during the past century its prominence has been displaced by modern therapeutics. Recently, attention has been drawn to arsenic by its dramatic clinical efficacy against acute promyelocytic leukemia. Although toxic reactiv...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0306687101

    authors: Chou WC,Jie C,Kenedy AA,Jones RJ,Trush MA,Dang CV

    更新日期:2004-03-30 00:00:00

  • Cooperative enhancement of specificity in a lattice of T cell receptors.

    abstract::Two of the most important models to account for the specificity and sensitivity of the T cell receptor (TCR) are the kinetic proofreading and serial ligation models. However, although kinetic proofreading provides a means for individual TCRs to measure accurately the length of time they are engaged and signal appropri...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.101113698

    authors: Chan C,George AJ,Stark J

    更新日期:2001-05-08 00:00:00

  • Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis.

    abstract::Arachidonic acid (AA) metabolites derived from both cyclooxygenase (COX) and lipoxygenase (LOX) pathways transduce a variety of signals related to cell growth. Here, we report that the AA LOX pathway also functions as a critical regulator of cell survival and apoptosis. Rat Walker 256 (W256) carcinosarcoma cells expre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.11.5241

    authors: Tang DG,Chen YQ,Honn KV

    更新日期:1996-05-28 00:00:00

  • Nerve growth factor modulates the drug sensitivity of neurotransmitter release from PC-12 cells.

    abstract::The release of catecholamines from adrenal chromaffin cells is known to be blocked by dihydropyridines, such as nitrendipine, and enhanced by others, such as BAY K8644. On the other hand, release from sympathetic neurons is predominantly insensitive to these agents. Release of [3H]norepinephrine from undifferentiated ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.7.2243

    authors: Kongsamut S,Miller RJ

    更新日期:1986-04-01 00:00:00

  • Extrachromosomal copies of transposon Tc1 in the nematode Caenorhabditis elegans.

    abstract::Extrachromosomal copies of the 1.6-kilobase transposable element Tc1 are present at the level of between 0.1 and 1.0 copy per cell in Caenorhabditis elegans strain Bergerac. Extrachromosomal elements were detected and studied using Southern hybridizations employing a Tc1-specific probe. The amount of extrachromosomal ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.13.4018

    authors: Ruan K,Emmons SW

    更新日期:1984-07-01 00:00:00

  • Integration of stress-related and reactive oxygen species-mediated signals by Topoisomerase VI in Arabidopsis thaliana.

    abstract::Environmental stress often leads to an increased production of reactive oxygen species that are involved in plastid-to-nucleus retrograde signaling. Soon after the release of singlet oxygen ((1)O(2)) in chloroplasts of the flu mutant of Arabidopsis, reprogramming of nuclear gene expression reveals a rapid transfer of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1202041109

    authors: Simková K,Moreau F,Pawlak P,Vriet C,Baruah A,Alexandre C,Hennig L,Apel K,Laloi C

    更新日期:2012-10-02 00:00:00

  • Binding properties of a cell adhesion molecule from neural tissue.

    abstract::We have previously identified and purified a cell surface glycoprotein from retina and brain, called neural cell adhesion molecule or N-CAM, that appears to be involved in neural cell--cell adhesion, the fasciculation of neurites, and the formation of normal tissue patterns in the retina. The present studies reveal th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.2.685

    authors: Rutishauser U,Hoffman S,Edelman GM

    更新日期:1982-01-01 00:00:00