Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia
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Sandrine Poglio1,2,3,4, Daniel Lewandowski2,3,4,5, Julien Calvo1,2,3,4, Aurélie Caye6,7, Audrey Gros8,9, Elodie Laharanne8,9, Thierry Leblanc10, Judith Landman-Parker11, André Baruchel10, Jean Soulier6,12,13, Paola Ballerini1,2,3,4,11, Emmanuelle Clappier6,12,13, Françoise Pflumio1,2,3,4
1Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), DSV-IRCM-SCSR-LSHL, UMR 967, Fontenay-aux-Roses, France
2INSERM, U967, Fontenay-aux-Roses, France
3Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France
4Université Paris-Sud, UMR 967, Fontenay-aux-Roses, France
5CEA, DSV-IRCM-SCSR-LRTS, UMR 967, Fontenay-aux-Roses, France
6Université Paris Diderot, Paris, France
7Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, UF de Génétique Moléculaire, Hôpital Robert Debré Paris, France
8INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Bordeaux, France
9Université de Bordeaux, Bordeaux, France
10AP-HP, Service d’hématologie Pédiatrique, Hôpital Robert Debré, Paris, France
11AP-HP, Service d’hématologie Pédiatrique, Hôpital Armand Trousseau, Paris, France
12AP-HP, Laboratoire d’Hématologie, Hôpital Saint-Louis, Paris, France
13Team Genome and Cancer, U944 INSERM, Paris, France
Françoise Pflumio, email: email@example.com
Sandrine Poglio, email: firstname.lastname@example.org
Keywords: T-ALL, leukemia initiating cells, clonal selection, CD34, xenograft
Received: June 29, 2015 Accepted: April 22, 2016 Published: May 12, 2016
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.
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