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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4173-4180. Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2003-11-3944. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3944v1 104/13/4173    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Asnafi, V. Articles by Macintyre, E. Search for Related Content PubMed PubMed Citation Articles by Asnafi, V. Articles by Macintyre, E. Related Collections Immunobiology Neoplasia Oncogenes and Tumor Suppressors Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy Vahid Asnafi, Kheira Beldjord, Marta Libura, Patrick Villarese, Corrine Millien, Paola Ballerini, Emilienne Kuhlein, Marina Lafage-Pochitaloff, Eric Delabesse, Olivier Bernard, and Elizabeth Macintyre From the Necker-Enfants-Malades and Trousseau, Assistance Publique-Hopitaux de Paris (AP-HP), INSERM EMIU210 and Université Paris V, Hôpital Purpan, Toulouse, France; and Institut Paoli Calmettes, Université de la Méditerranée, Marseille, France. Postnatal thymic involution occurs progressively throughout the first 3 decades of life. It predominantly affects T-cell receptor (TCR) -lineage precursors, with a consequent proportional increase in multipotent thymic precursors. We show that T-acute lymphoblastic leukemias (T-ALLs) demonstrate a similar shift with age from predominantly TCR expressing to an immature (IM0//) stage of maturation arrest. Half demonstrate HOX11, HOX11L2, SIL-TAL1, or CALM-AF10 deregulation, with each being associated with a specific, age-independent stage of maturation arrest. HOX11 and SIL-TAL represent -lineage oncogenes, whereas HOX11L2 expression identifies an intermediate /-lineage stage of maturation arrest. In keeping with preferential -lineage involution, the incidence of SIL-TAL1 and HOX11L2 deregulation decreased with age. In contrast, HOX11 deregulation became more frequent, suggesting longer latency. TAL1/LMO1 deregulation is more frequent in -lineage T-ALL, when it is predominantly due to SIL-TAL1 rearrangements in children but to currently unknown mechanisms in adolescents and adults. LMO2 was more frequently coexpressed with LYL1, predominantly in IM0// adult cases, than with TAL1. These age-related changes in phenotype and oncogenic pathways probably reflect progressive changes in the thymic population at risk of malignant transformation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Baleydier, A.-V. Decouvelaere, J. Bergeron, P. Gaulard, D. Canioni, Y. Bertrand, S. Lepretre, B. Petit, H. Dombret, K. Beldjord, et al. T Cell Receptor Genotyping and HOXA/TLX1 Expression Define Three T Lymphoblastic Lymphoma Subsets which Might Affect Clinical Outcome Clin. Cancer Res., February 1, 2008; 14(3): 692 - 700. [Abstract] [Full Text] [PDF] K. Bessette, M. L. Lang, R. A. Fava, M. Grundy, J. Heinen, L. Horne, R. Spolski, A. Al-Shami, H. C. Morse III, W. J. Leonard, et al. A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling Blood, January 1, 2008; 111(1): 344 - 350. [Abstract] [Full Text] [PDF] J. R. Gothert, R. L. Brake, M. Smeets, U. Duhrsen, C. G. Begley, and D. J. Izon NOTCH1 pathway activation is an early hallmark of SCL T leukemogenesis Blood, November 15, 2007; 110(10): 3753 - 3762. [Abstract] [Full Text] [PDF] J. Bergeron, E. Clappier, I. Radford, A. Buzyn, C. Millien, G. Soler, P. Ballerini, X. Thomas, J. Soulier, H. Dombret, et al. Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs Blood, October 1, 2007; 110(7): 2324 - 2330. [Abstract] [Full Text] [PDF] W. Y. I. Chan, G. A. Follows, G. Lacaud, J. E. Pimanda, J.-R. Landry, S. Kinston, K. Knezevic, S. Piltz, I. J. Donaldson, L. Gambardella, et al. The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype Blood, March 1, 2007; 109(5): 1908 - 1916. [Abstract] [Full Text] [PDF] Y. Natkunam, S. Zhao, D. Y. Mason, J. Chen, B. Taidi, M. Jones, A. S. Hammer, S. Hamilton Dutoit, I. S. Lossos, and R. Levy The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas Blood, February 15, 2007; 109(4): 1636 - 1642. [Abstract] [Full Text] [PDF] J. Soulier, E. Clappier, J.-M. Cayuela, A. Regnault, M. Garcia-Peydro, H. Dombret, A. Baruchel, M.-L. Toribio, and F. Sigaux HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL) Blood, July 1, 2005; 106(1): 274 - 286. [Abstract] [Full Text] [PDF] V. Asnafi, A. Buzyn, X. Thomas, F. Huguet, N. Vey, J.-M. Boiron, O. Reman, J.-M. Cayuela, V. Lheritier, J.-P. Vernant, et al. Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study Blood, April 15, 2005; 105(8): 3072 - 3078. [Abstract] [Full Text] [PDF]

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