Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia
Autor: | André Baruchel, Judith Landman-Parker, Daniel Lewandowski, Paola Ballerini, Jean Soulier, Thierry Leblanc, Sandrine Poglio, Audrey Gros, Elodie Laharanne, Julien Calvo, Françoise Pflumio, Aurélie Caye, Emmanuelle Clappier |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Human leukemia Time Factors T cell Lymphoblastic Leukemia Transplantation Heterologous Mice Nude Antigens CD34 Mice Transgenic Mice SCID Newly diagnosed Precursor T-Cell Lymphoblastic Leukemia-Lymphoma clonal selection Genetic Heterogeneity Mice Young Adult 03 medical and health sciences Mice Inbred NOD hemic and lymphatic diseases Cell Line Tumor medicine Animals Humans xenograft Child Translational oncology business.industry Genetic Variation leukemia initiating cells medicine.disease Molecular biology 3. Good health Leukemia 030104 developmental biology medicine.anatomical_structure Oncology Immunology Disease Progression Heterografts Genetic selection CD34 T-ALL business Neoplasm Transplantation Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | // Sandrine Poglio 1, 2, 3, 4 , Daniel Lewandowski 2, 3, 4, 5 , Julien Calvo 1, 2, 3, 4 , Aurelie Caye 6, 7 , Audrey Gros 8, 9 , Elodie Laharanne 8, 9 , Thierry Leblanc 10 , Judith Landman-Parker 11 , Andre Baruchel 10 , Jean Soulier 6, 12, 13 , Paola Ballerini 1, 2, 3, 4, 11 , Emmanuelle Clappier 6, 12, 13 , Francoise Pflumio 1, 2, 3, 4 1 Commissariat a l’Energie Atomique et aux Energies Alternatives (CEA), DSV-IRCM-SCSR-LSHL, UMR 967, Fontenay-aux-Roses, France 2 INSERM, U967, Fontenay-aux-Roses, France 3 Universite Paris Diderot, Sorbonne Paris Cite, UMR 967, Fontenay-aux-Roses, France 4 Universite Paris-Sud, UMR 967, Fontenay-aux-Roses, France 5 CEA, DSV-IRCM-SCSR-LRTS, UMR 967, Fontenay-aux-Roses, France 6 Universite Paris Diderot, Paris, France 7 Assistance Publique-Hopitaux de Paris (AP-HP), Departement de Genetique, UF de Genetique Moleculaire, Hopital Robert Debre Paris, France 8 INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Bordeaux, France 9 Universite de Bordeaux, Bordeaux, France 10 AP-HP, Service d’hematologie Pediatrique, Hopital Robert Debre, Paris, France 11 AP-HP, Service d’hematologie Pediatrique, Hopital Armand Trousseau, Paris, France 12 AP-HP, Laboratoire d’Hematologie, Hopital Saint-Louis, Paris, France 13 Team Genome and Cancer, U944 INSERM, Paris, France Correspondence to: Francoise Pflumio, email: francoise.pflumio@cea.fr Sandrine Poglio, email: sandrine.poglio@u-bordeaux.fr Keywords: T-ALL, leukemia initiating cells, clonal selection, CD34, xenograft Received: June 29, 2015 Accepted: April 22, 2016 Published: May 12, 2016 ABSTRACT T cell acute lymphoblastic leukemia (T-ALL) develops through accumulation of multiple genomic alterations within T-cell progenitors resulting in clonal heterogeneity among leukemic cells. Human T-ALL xeno-transplantation in immunodeficient mice is a gold standard approach to study leukemia biology and we recently uncovered that the leukemia development is more or less rapid depending on T-ALL sample. The resulting human leukemia may arise through genetic selection and we previously showed that human T-ALL development in immune-deficient mice is significantly enhanced upon CD7 + /CD34 + leukemic cell transplantations. Here we investigated the genetic characteristics of CD7 + /CD34 + and CD7 + /CD34 − cells from newly diagnosed human T-ALL and correlated it to the speed of leukemia development. We observed that CD7 + /CD34 + or CD7 + /CD34 − T-ALL cells that promote leukemia within a short-time period are genetically similar, as well as xenograft-derived leukemia resulting from both cell fractions. In the case of delayed T-ALL growth CD7 + /CD34 + or CD7 + /CD34 − cells were either genetically diverse, the resulting xenograft leukemia arising from different but branched subclones present in the original sample, or similar, indicating decreased fitness to mouse micro-environment. Altogether, our work provides new information relating the speed of leukemia development in xenografts to the genetic diversity of T-ALL cell compartments. |
Databáze: | OpenAIRE |
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