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INFANTLEUKEMIA SIGNED
GENOMIC, CELLULAR AND DEVELOPMENTAL RECONSTRUCTION OFINFANT MLL-AF4+ ACUTE LYMPHOBLASTIC LEUKEMIA
Total Cost €
0EC-Contrib. €
0Partnership
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0INFANTLEUKEMIA 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.
progression
variegated
blasts
absence
nature
treatment
genomic
questions
functional
cohort
precise
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progenitor
human
ma4
genetics
elusive
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stability
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biology
exome
xenografts
cancer
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hspcs
hierarchical
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infant
lymphoblastic
omics
serial
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models
methylation
strategies
seq
data
mediated
cns
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rapid
paired
twins
breaking
leukemogenic
h3k79
stochastic
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heterogeneity
cell
developmental
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combined
leukemia
suggest
100
disease
concordance
drivers
assays
unprecedented
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hallmark
genome
adult
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prenatal
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stem
model
uniquely
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therapy
all
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acute
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epigenetics
faithfully
diagnostic
hypothesize
lic
lack
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Project "INFANTLEUKEMIA" data sheet
The following table provides information about the project.
| Coordinator |
FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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, ElÃas 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-MartÃnez, Matteo L. Baroni, Francisco Gutierrez-Agüera, Heleia Roca-Ho, Oscar Blanch-Lombarte, Sara González-GarcÃa, Montserrat Torrebadell, Jordi Junca, Manuel RamÃrez-Orellana, TalÃa Velasco-Hernández, Clara Bueno, José LuÃs Fuster, Julia G. Prado, Julien Calvo, Benjamin Uzan, Jan Cools, Mireia Camos, Françoise Pflumio, MarÃa 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 DÃaz de la Guardia, Jordi Ribera, Lurdes Zamora, Chrystele Bilhou-Nabera, Nassera Abermil, Hélène Guermouche, Elodie Gouache, Guy Leverger, Mario F. Fraga, AgustÃn 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 RodrÃguez-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 GarcÃa-Toraño, Raúl F Perez, MarÃa G GarcÃa, Antonella Carella, Patricia C Pruneda, Cristina Prieto, Marija Dmitrijeva, Pablo Santamarina, ThalÃa 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-RuÃz, 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 RodrÃguez-Baena, A Sanjuan-Pla, V Ayllón, M RamÃrez, M Bardini, P De Lorenzo, M G Valsecchi, M Stanulla, M Iglesias, P Ballerini, à M Carcaboso, J Mora, F Locatelli, A Bertaina, L Padilla, J Carlos RodrÃguez-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, AgustÃn F. Fernandez, Mahito Nakanishi, Raúl Torres-Ruiz, Sandra RodrÃguez-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. RodrÃguez-Gómez, Vanesa Ruiz-Bonilla, Clara Bueno, Patricia González-RodrÃguez, 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-MejÃa, Antonio Agraz-Doblas, Ignacio Varela, Marcus Buschbeck, Anna Palau, Xonia Carvajal-Vergara, Alessandra Giorgetti, Anthony Ford, Majlinda Lako, Isabel Granada, Neus Ruiz-Xivillé, Sandra RodrÃguez-Perales, Raul Torres-RuÃz, 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 DÃaz 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 MarÃn, 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 |
Ãlvaro 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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