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INFANTLEUKEMIA SIGNED

GENOMIC, CELLULAR AND DEVELOPMENTAL RECONSTRUCTION OFINFANT MLL-AF4+ ACUTE LYMPHOBLASTIC LEUKEMIA

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 INFANTLEUKEMIA project word cloud

Explore the words cloud of the INFANTLEUKEMIA project. It provides you a very rough idea of what is the project "INFANTLEUKEMIA" about.

multilayer    lic    nature    clonal    precise    resistance    locus    matched    seq    therapy    methylation    model    models    mediated    prognosis    hematopoietic    transcriptome    onset    prospective    remission    exome    adult    stochastic    patient    cells    samples    uniquely    h3k79    heterogeneity    epigenetics    variegated    follow    underlying    rapid    threatening    cell    reproduce    hspcs    life    platform    dna    paired    all    progressively    involvement    genetics    profiles    breaking    landscape    mll    strategies    questions    functional    hspc    genome    blasts    treatment    diagnostic    xenografts    acute    data    elusive    ma4    infant    allele    100    assays    vs    human    hypothesize    mutational    leukemia    absence    lymphoblastic    biology    hallmark    intriguing    extremely    ground    developmental    progenitor    rearrangement    cas9    dismal    underlie    omics    cancer    combined    stability    disease    unprecedented    drivers    prenatal    serial    progression    function    initiating    concordance    transformed    af4    cohort    suggest    scrutinize    stem    hierarchical    surprising    crispr    faithfully    genomic    integration    cns    perform    oncogenic    11    lack    twins    leukemogenic   

Project "INFANTLEUKEMIA" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS 

Organization address
address: CARRER MUNTANER 383 3/2
city: BARCELONA
postcode: 8021
website: www.carrerasresearch.org

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Project website http://www.carrerasresearch.org/es/Stem_cells_mesenchymal_cancer_and_development
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS ES (BARCELONA) coordinator 2˙000˙000.00

Map

 Project objective

Infant cancer is very distinct to adult cancer and it is progressively seen as a developmental disease. An intriguing infant cancer is the t(4;11) acute lymphoblastic leukemia (ALL) characterized by the hallmark rearrangement MLL-AF4 (MA4), and associated with dismal prognosis. The 100% concordance in twins and its prenatal onset suggest an extremely rapid disease progression. Many key issues remain elusive: Is MA4 leukemogenic? Which are other relevant oncogenic drivers? Which is the nature of the cell transformed by MA4? Which is the leukemia-initiating cell (LIC)? Does this ALL follow a hierarchical or stochastic cancer model? How to explain therapy resistance and CNS involvement? To what extent do genetics vs epigenetics contribute this ALL?

These questions remain a challenge due to: 1) the absence of prospective studies on diagnostic/remission-matched samples, 2) the lack of models which faithfully reproduce the disease and 3) a surprising genomic stability of this ALL.

I hypothesize that a Multilayer-Omics to function approach in patient blasts and early human hematopoietic stem/progenitor cells (HSPC) is required to fully scrutinize the biology underlying this life-threatening leukemia. I will perform genome-wide studies on the mutational landscape, DNA and H3K79 methylation profiles, and transcriptome on a uniquely available, large cohort of diagnostic/remission-matched samples. Omics data integration will provide unprecedented information about oncogenic drivers which must be analyzed in ground-breaking functional assays using patient blasts and early HSPCs carrying a CRISPR/Cas9-mediated locus/allele-specific t(4;11). Serial xenografts combined with exome-seq in paired diagnostic samples and xenografts will identify the LIC and determine whether variegated genetics may underlie clonal functional heterogeneity. This project will provide a precise understanding and a disease model for MA4 ALL, offering a platform for new treatment strategies.

 Publications

year authors and title journal last update
List of publications.
2019 Antonio Agraz-Doblas, Clara Bueno, Rachael Bashford-Rogers, Anindita Roy, Pauline Schneider, Michela Bardini, Paola Ballerini, Gianni Cazzaniga, Thaidy Moreno, Carlos Revilla, Marta Gut, Maria G. Valsecchi, Irene Roberts, Rob Pieters, Paola De Lorenzo, Ignacio Varela, Pablo Menendez, Ronald W. Stam
Unraveling the cellular origin and clinical prognostic markers of infant B-cell acute lymphoblastic leukemia using genome-wide analysis
published pages: 1176-1188, ISSN: 0390-6078, DOI: 10.3324/haematol.2018.206375
Haematologica 104/6 2020-02-06
2019 Anna Vidal-Crespo, Alba Matas-Céspedes, Vanina Rodriguez, Cédric Rossi, Juan G. Valero, Neus Serrat, Alejandra Sanjuan Pla, Pablo Menéndez, Gaël Roué, Armando López-Guillermo, Eva Giné, Elías Campo, Dolors Colomer, Christine Bezombes, Jeroen Lammerts van Bueren, Christopher Chiu, Parul Doshi, Patricia Pérez-Galán
Daratumumab displays in vitro and in vivo anti-tumor activity in models of B cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens
published pages: haematol.2018.21, ISSN: 0390-6078, DOI: 10.3324/haematol.2018.211904
Haematologica 11th July 2019 2020-02-06
2019 Sorcha O’Byrne, Natalina Elliott, Siobhan Rice, Gemma Buck, Nicholas Fordham, Catherine Garnett, Laura Godfrey, Nicholas T. Crump, Gary Wright, Sarah Inglott, Peng Hua, Bethan Psaila, Benjamin Povinelli, David J. H. F. Knapp, Antonio Agraz-Doblas, Clara Bueno, Ignacio Varela, Phillip Bennett, Hashem Koohy, Suzanne M. Watt, Anastasios Karadimitris, Adam J. Mead, Phillip Ancliff, Paresh Vyas, Pabl
Discovery of a CD10-negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs
published pages: 1059-1071, ISSN: 0006-4971, DOI: 10.1182/blood.2019001289
Blood 134/13 2020-02-06
2019 Diego Sánchez-Martínez, Matteo L. Baroni, Francisco Gutierrez-Agüera, Heleia Roca-Ho, Oscar Blanch-Lombarte, Sara González-García, Montserrat Torrebadell, Jordi Junca, Manuel Ramírez-Orellana, Talía Velasco-Hernández, Clara Bueno, José Luís Fuster, Julia G. Prado, Julien Calvo, Benjamin Uzan, Jan Cools, Mireia Camos, Françoise Pflumio, María Luisa Toribio, Pablo Menéndez
Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia
published pages: 2291-2304, ISSN: 0006-4971, DOI: 10.1182/blood-2018-10-882944
Blood 133/21 2020-02-06
2019 Clara Bueno, Fernando J Calero-Nieto, Xiaonan Wang, Rafael Valdés-Mas, Francisco Gutiérrez-Agüera, Heleia Roca-Ho, Veronica Ayllon, Pedro J Real, David Arambilet, Lluis Espinosa, Raul Torres-Ruiz, Antonio Agraz-Doblas, Ignacio Varela, Jasper de Boer, Anna Bigas, Bertie Gottgens, Rolf Marschalek, Pablo Menendez
Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation between AF4-MLL and MLL-AF4 fusions
published pages: 1189-1201, ISSN: 0390-6078, DOI: 10.3324/haematol.2018.202044
Haematologica 104/6 2020-02-06
2019 Clara Bueno, J. Ramón Tejedor, Rachael Bashford-Rogers, Laura González-Silva, Rafael Valdés-Mas, Antonio Agraz-Doblás, Rafael Díaz de la Guardia, Jordi Ribera, Lurdes Zamora, Chrystele Bilhou-Nabera, Nassera Abermil, Hélène Guermouche, Elodie Gouache, Guy Leverger, Mario F. Fraga, Agustín F. Fernández, Paola Ballerini, Ignacio Varela, Pablo Menendez
Natural history and cell of origin of TCF3-ZNF384 and PTPN11 mutations in monozygotic twins with concordant BCP-ALL
published pages: 900-905, ISSN: 0006-4971, DOI: 10.1182/blood.2019000893
Blood 134/11 2020-02-06
2019 Julio Castaño, Sergi Aranda, Clara Bueno, Fernando J. Calero-Nieto, Eva Mejia-Ramirez, Jose Luis Mosquera, Enrique Blanco, Xiaonan Wang, Cristina Prieto, Lorea Zabaleta, Elisabetta Mereu, Meritxell Rovira, Senda Jiménez-Delgado, Daniel R. Matson, Holger Heyn, Emery H. Bresnick, Berthold Göttgens, Luciano Di Croce, Pablo Menendez, Angel Raya, Alessandra Giorgetti
GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm
published pages: 515-529, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2019.07.009
Stem Cell Reports 13/3 2020-02-06
2020 Rafael Diaz de la Guardia, Laura González-Silva, Belén López-Millán, Juan José Rodríguez-Sevilla, Matteo L. Baroni, Clara Bueno, Eduardo Anguita, Susana Vives, Laura Palomo, Helene Lapillonne, Ignacio Varela, Pablo Menendez
Bone Marrow Clonogenic Myeloid Progenitors from NPM1-Mutated AML Patients Do Not Harbor the NPM1 Mutation: Implication for the Cell-Of-Origin of NPM1+ AML
published pages: 73, ISSN: 2073-4425, DOI: 10.3390/genes11010073
Genes 11/1 2020-02-06
2019 Rocio G Urdinguio, Virginia Lopez, Gustavo F Bayón, Rafael Diaz de la Guardia, Marta I Sierra, Estela García-Toraño, Raúl F Perez, María G García, Antonella Carella, Patricia C Pruneda, Cristina Prieto, Marija Dmitrijeva, Pablo Santamarina, Thalía Belmonte, Cristina Mangas, Elena Diaconu, Cecilia Ferrero, Juan Ramón Tejedor, Juan Luis Fernandez-Morera, Cristina Bravo, Clara Bueno, Aleja
Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment
published pages: 5016-5037, ISSN: 0305-1048, DOI: 10.1093/nar/gkz195
Nucleic Acids Research 47/10 2020-02-06
2017 Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R. Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L. Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes
published pages: 1573-1586, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2017.04.019
Stem Cell Reports 8/6 2019-05-31
2017 Clara Bueno, Pablo Menendez
Human acute leukemia induced pluripotent stem cells: a unique model for investigating disease development and pathogenesis
published pages: 55-55, ISSN: 2313-0792, DOI: 10.21037/sci.2017.05.12
Stem Cell Investigation 4/7 2019-05-31
2017 Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The AF4-MLL fusion transiently augments multilineage hematopoietic engraftment but is not sufficient to initiate leukemia in cord blood CD34+ cells
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.19567
Oncotarget 8/47 2019-05-31
2017 Ignacio Varela, Pablo Menendez, Alejandra Sanjuan-Pla
Intratumoral heterogeneity and clonal evolution in blood malignancies and solid tumors
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.20279
Oncotarget 8/39 2019-05-31
2016 Julio Castaño, Ana B. Herrero, Aldeheid Bursen, Federico González, Rolf Marschalek, Norma C. Gutiérrez, Pablo Menendez
Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.8938
Oncotarget 7/21 2019-05-31
2018 Katrin Ottersbach, Alejandra Sanjuan-Pla, Raúl Torres-Ruíz, Clara Bueno, Talia Velasco-Hernández, Pablo Menendez
The “Never-Ending” Mouse Models for MLL-Rearranged Acute Leukemia Are Still Teaching Us
published pages: e57, ISSN: 2572-9241, DOI: 10.1097/HS9.0000000000000057
HemaSphere 2/4 2019-05-31
2018 Pablo Menendez, Rafael Diaz de la Guardia, Belen Lopez-Millan
BM-Mscs From Risk-Stratified AML Patients Support Normal Hematopoiesis and are Anti-Inflammatory in in Vivo Preclinical Models of Hematopoietic Reconstitution and Severe Colitis
published pages: S85, ISSN: 0301-472X, DOI: 10.1016/j.exphem.2018.06.091
Experimental Hematology 64 2019-05-31
2017 Damià Romero-Moya, Julio Castaño, Carlos Santos-Ocaña, Plácido Navas, Pablo Menendez
Generation, genome edition and characterization of iPSC lines from a patient with coenzyme Q 10 deficiency harboring a heterozygous mutation in COQ4 gene
published pages: 144-147, ISSN: 1873-5061, DOI: 10.1016/j.scr.2016.09.007
Stem Cell Research 24 2019-05-31
2017 C Prieto, B López-Millán, H Roca-Ho, R W Stam, D Romero-Moya, F J Rodríguez-Baena, A Sanjuan-Pla, V Ayllón, M Ramírez, M Bardini, P De Lorenzo, M G Valsecchi, M Stanulla, M Iglesias, P Ballerini, Á M Carcaboso, J Mora, F Locatelli, A Bertaina, L Padilla, J Carlos Rodríguez-Manzaneque, C Bueno, P Menéndez
NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL
published pages: 633-644, ISSN: 0887-6924, DOI: 10.1038/leu.2017.294
Leukemia 32/3 2019-05-31
2017 Julio Castaño, Clara Bueno, Senda Jiménez-Delgado, Heleia Roca-Ho, Mario F. Fraga, Agustín F. Fernandez, Mahito Nakanishi, Raúl Torres-Ruiz, Sandra Rodríguez-Perales, Pablo Menéndez
Generation and characterization of a human iPSC cell line expressing inducible Cas9 in the “safe harbor” AAVS1 locus
published pages: 137-140, ISSN: 1873-5061, DOI: 10.1016/j.scr.2017.04.011
Stem Cell Research 21 2019-05-31
2017 Damià Romero-Moya, Carlos Santos-Ocaña, Julio Castaño, Gloria Garrabou, José A. Rodríguez-Gómez, Vanesa Ruiz-Bonilla, Clara Bueno, Patricia González-Rodríguez, Alessandra Giorgetti, Eusebio Perdiguero, Cristina Prieto, Constanza Moren-Nuñez, Daniel J. Fernández-Ayala, Maria Victoria Cascajo, Iván Velasco, Josep Maria Canals, Raquel Montero, Delia Yubero, Cristina Jou, José López-Barneo, Francesc Cardellach, Pura Muñoz-Cánoves, Rafael Artuch, Plácido Navas, Pablo Menendez
Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q 10 Deficiency
published pages: 1687-1703, ISSN: 1066-5099, DOI: 10.1002/stem.2634
STEM CELLS 35/7 2019-05-31
2016 Alvaro Muñoz-López, Damià Romero-Moya, Cristina Prieto, Verónica Ramos-Mejía, Antonio Agraz-Doblas, Ignacio Varela, Marcus Buschbeck, Anna Palau, Xonia Carvajal-Vergara, Alessandra Giorgetti, Anthony Ford, Majlinda Lako, Isabel Granada, Neus Ruiz-Xivillé, Sandra Rodríguez-Perales, Raul Torres-Ruíz, Ronald W. Stam, Jose Luis Fuster, Mario F. Fraga, Mahito Nakanishi, Gianni Cazzaniga, Michela Bardini, Isabel Cobo, Gustavo F. Bayon, Agustin F. Fernandez, Clara Bueno, Pablo Menendez
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency
published pages: 602-618, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2016.08.013
Stem Cell Reports 7/4 2019-05-31
2017 Oscar Navarro-Montero, Veronica Ayllon, Mar Lamolda, Lourdes López-Onieva, Rosa Montes, Clara Bueno, Elizabeth Ng, Xiomara Guerrero-Carreno, Tamara Romero, Damià Romero-Moya, Ed Stanley, Andrew Elefanty, Verónica Ramos-Mejia, Pablo Menendez, Pedro J. Real
RUNX1c Regulates Hematopoietic Differentiation of Human Pluripotent Stem Cells Possibly in Cooperation with Proinflammatory Signaling
published pages: 2253-2266, ISSN: 1066-5099, DOI: 10.1002/stem.2700
STEM CELLS 35/11 2019-05-31
2017 Alessandra Giorgetti, Julio Castaño, Clara Bueno, Rafael Díaz de la Guardia, Mario Delgado, Anna Bigas, Lluis Espinosa, Pablo Menendez
Proinflammatory signals are insufficient to drive definitive hematopoietic specification of human HSCs in vitro
published pages: 85-93.e2, ISSN: 0301-472X, DOI: 10.1016/j.exphem.2016.09.007
Experimental Hematology 45 2019-05-31
2017 Raúl Torres-Ruiz, Sandra Rodriguez-Perales, Clara Bueno, Pablo Menendez
Modeling mixed-lineage-rearranged leukemia initiation in CD34 + cells: a “CRISPR” solution
published pages: 1467-1468, ISSN: 0390-6078, DOI: 10.3324/haematol.2017.173740
Haematologica 102/9 2019-05-31
2017 Angela Macia, Thomas J. Widmann, Sara R. Heras, Veronica Ayllon, Laura Sanchez, Meriem Benkaddour-Boumzaouad, Martin Muñoz-Lopez, Alejandro Rubio, Suyapa Amador-Cubero, Eva Blanco-Jimenez, Javier Garcia-Castro, Pablo Menendez, Philip Ng, Alysson R. Muotri, John L. Goodier, Jose L. Garcia-Perez
Engineered LINE-1 retrotransposition in nondividing human neurons
published pages: 335-348, ISSN: 1088-9051, DOI: 10.1101/gr.206805.116
Genome Research 27/3 2019-05-31
2016 Alejandra Sanjuan-Pla, Damia Romero-Moya, Cristina Prieto, Clara Bueno, Anna Bigas, Pablo Menendez
Intra-Bone Marrow Transplantation Confers Superior Multilineage Engraftment of Murine Aorta-Gonad Mesonephros Cells Over Intravenous Transplantation
published pages: 259-265, ISSN: 1547-3287, DOI: 10.1089/scd.2015.0309
Stem Cells and Development 25/3 2019-05-31
2016 A. Engert, C. Balduini, A. Brand, B. Coiffier, C. Cordonnier, H. Dohner, T. D. de Wit, S. Eichinger, W. Fibbe, T. Green, F. de Haas, A. Iolascon, T. Jaffredo, F. Rodeghiero, G. Salles, J. J. Schuringa, J. J. Schuringa, T. Jaffredo, B. Coiffier, G. Salles, H. Dohner, A. Iolascon, C. Balduini, S. Eichinger, A. Brand, C. Cordonnier, W. Fibbe
The European Hematology Association Roadmap for European Hematology Research: a consensus document
published pages: 115-208, ISSN: 0390-6078, DOI: 10.3324/haematol.2015.136739
Haematologica 101/2 2019-05-31
2017 Olavi Pelkonen, Andrea Terron, Antonio F. Hernandez, Pablo Menendez, Susanne Hougaard Bennekou
Chemical exposure and infant leukaemia: development of an adverse outcome pathway (AOP) for aetiology and risk assessment research
published pages: 2763-2780, ISSN: 0340-5761, DOI: 10.1007/s00204-017-1986-x
Archives of Toxicology 91/8 2019-05-31
2016 Cristina Prieto, Ronald W. Stam, Antonio Agraz-Doblas, Paola Ballerini, Mireia Camos, Julio Castaño, Rolf Marschalek, Aldeheid Bursen, Ignacio Varela, Clara Bueno, Pablo Menendez
Activated KRAS Cooperates with MLL-AF4 to Promote Extramedullary Engraftment and Migration of Cord Blood CD34 + HSPC But Is Insufficient to Initiate Leukemia
published pages: 2478-2489, ISSN: 0008-5472, DOI: 10.1158/0008-5472.CAN-15-2769
Cancer Research 76/8 2019-05-31
2018 Belen Lopez-Millan, Rafael Diaz de la Guardia, Heleia Roca-Ho, Eduardo Anguita, Abul B. M. M. K. Islam, Damia Romero-Moya, Cristina Prieto, Francisco Gutierrez-Agüera, Jose Antonio Bejarano-Garcia, Jose Antonio Perez-Simon, Paula Costales, Montse Rovira, Pedro Marín, Silvia Menendez, Mar Iglesias, Jose Luis Fuster, Alvaro Urbano-Ispizua, Fernando Anjos-Afonso, Clara Bueno, Pablo Menendez
IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML
published pages: 1-14, ISSN: 2162-402X, DOI: 10.1080/2162402x.2018.1477460
OncoImmunology 2019-05-31
2016 Álvaro Muñoz-López, Eddy. H.J. van Roon, Damià Romero-Moya, Belén López-Millan, Ronald W. Stam, Dolors Colomer, Mahito Nakanishi, Clara Bueno, Pablo Menendez
Cellular Ontogeny and Hierarchy Influence the Reprogramming Efficiency of Human B Cells into Induced Pluripotent Stem Cells
published pages: 581-587, ISSN: 1066-5099, DOI: 10.1002/stem.2303
STEM CELLS 34/3 2019-05-31

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