title: Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia.
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.
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), DSV-IRCM-SCSR-LSHL, UMR 967, Fontenay-aux-Roses, France.|INSERM, U967, Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France.|Université Paris-Sud, UMR 967, Fontenay-aux-Roses, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Poglio
authors.affiliation: INSERM, U967, Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France.|Université Paris-Sud, UMR 967, Fontenay-aux-Roses, France.|CEA, DSV-IRCM-SCSR-LRTS, UMR 967, Fontenay-aux-Roses, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewandowski
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), DSV-IRCM-SCSR-LSHL, UMR 967, Fontenay-aux-Roses, France.|INSERM, U967, Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France.|Université Paris-Sud, UMR 967, Fontenay-aux-Roses, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Calvo
authors.affiliation: Université Paris Diderot, Paris, France.|Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, UF de Génétique Moléculaire, Hôpital Robert Debré Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Caye
authors.affiliation: INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Bordeaux, France.|Université de Bordeaux, Bordeaux, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gros
authors.affiliation: INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Bordeaux, France.|Université de Bordeaux, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Laharanne
authors.affiliation: AP-HP, Service d'hématologie Pédiatrique, Hôpital Robert Debré, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.affiliation: AP-HP, Service d'hématologie Pédiatrique, Hôpital Armand Trousseau, Paris, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Landman-Parker
authors.affiliation: AP-HP, Service d'hématologie Pédiatrique, Hôpital Robert Debré, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: Université Paris Diderot, Paris, France.|AP-HP, Laboratoire d'Hématologie, Hôpital Saint-Louis, Paris, France.|Team Genome and Cancer, U944 INSERM, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), DSV-IRCM-SCSR-LSHL, UMR 967, Fontenay-aux-Roses, France.|INSERM, U967, Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France.|Université Paris-Sud, UMR 967, Fontenay-aux-Roses, France.|AP-HP, Service d'hématologie Pédiatrique, Hôpital Armand Trousseau, Paris, France.
authors.forename: Paola
authors.initials: P
authors.lastname: Ballerini
authors.affiliation: Université Paris Diderot, Paris, France.|AP-HP, Laboratoire d'Hématologie, Hôpital Saint-Louis, Paris, France.|Team Genome and Cancer, U944 INSERM, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Clappier
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), DSV-IRCM-SCSR-LSHL, UMR 967, Fontenay-aux-Roses, France.|INSERM, U967, Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France.|Université Paris-Sud, UMR 967, Fontenay-aux-Roses, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Pflumio
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D018450:Disease Progression; D018740:Genetic Heterogeneity; D014644:Genetic Variation; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014183:Transplantation, Heterologous; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: CD34; T-ALL; clonal selection; leukemia initiating cells; xenograft