Portal de Periódicos da CAPES

Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia

2016; Impact Journals LLC; Volume: 7; Issue: 27 Linguagem: Inglês

10.18632/oncotarget.9313

1949-2553

Sandrine Poglio, Daniel Lewandowski, Julien Calvo, Aurélie Caye, Audrey Gros, Elodie Laharanne, Thierry Leblanc, Judith Landman‐Parker, André Baruchel, Jean Soulier, Paola Ballerini, Emmanuelle Clappier, Françoise Pflumio,

Chronic Myeloid Leukemia Treatments

// Sandrine Poglio 1, 2, 3, 4 , Daniel Lewandowski 2, 3, 4, 5 , Julien Calvo 1, 2, 3, 4 , Aurélie Caye 6, 7 , Audrey Gros 8, 9 , Elodie Laharanne 8, 9 , Thierry Leblanc 10 , Judith Landman-Parker 11 , André Baruchel 10 , Jean Soulier 6, 12, 13 , Paola Ballerini 1, 2, 3, 4, 11 , Emmanuelle Clappier 6, 12, 13 , Françoise Pflumio 1, 2, 3, 4 1 Commissariat à 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 Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France 4 Université Paris-Sud, UMR 967, Fontenay-aux-Roses, France 5 CEA, DSV-IRCM-SCSR-LRTS, UMR 967, Fontenay-aux-Roses, France 6 Université Paris Diderot, Paris, France 7 Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, UF de Génétique Moléculaire, Hôpital Robert Debré Paris, France 8 INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Bordeaux, France 9 Université de Bordeaux, Bordeaux, France 10 AP-HP, Service d'hématologie Pédiatrique, Hôpital Robert Debré, Paris, France 11 AP-HP, Service d'hématologie Pédiatrique, Hôpital Armand Trousseau, Paris, France 12 AP-HP, Laboratoire d'Hématologie, Hôpital Saint-Louis, Paris, France 13 Team Genome and Cancer, U944 INSERM, Paris, France Correspondence to: Françoise 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.