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Tumor associated antigen PRAME is a marker of favorable prognosis in childhood acute myeloid leukemia patients and modifies the expression of S100A4, Hsp 27, p21, IL-8 and IGFBP-2 in vitro and in vivo

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Tajeddine, Nicolas [UCL] Louis, Magali [UCL] Vermylen, Christiane [UCL] Gala, Jean-Luc [UCL] Tombal, Bertrand [UCL] Gailly, Philippe [UCL]

Preferentially expressed antigen of melanoma (PRAME) is expressed in a wide variety of tumors, but in contrast with most other tumor associated antigens, it is also expressed in leukemias. In a previous study, we showed that overexpression of PRAME induced apoptosis, inhibited cell proliferation and reduced tumorigenicity of leukemic cells in vivo. We also demonstrated that PRAME overexpression induced the repression of three genes (Hsp27, S100A4 and p21) associated with an unfavorable prognosis in leukemia. Here, we further investigated the mechanisms of PRAME-induced tumor suppression in vitro and in vivo. We performed a gene profiling study by analysing PRAME shRNA-silenced leukemic cells on high-density micro-arrays (Affymetrix) and found that PRAME altered the expression of two additional genes potentially involved in cancerogenesis and cancer progression: IL-8 and IGFBP-2. In a series of 28 acute myeloid leukemia pediatric patients, we observed that PRAME expression was associated with an increased leukemia-free survival. Importantly, the correlation between PRAME expression in leukemic cell lines and the decreased expression of Hsp27, S100A4, p21, IL-8 and the increased expression of IGFBP-2 was also observed in vivo, in leukemic patients. Our results suggest that the favorable prognosis of PRAME could be mediated, at least in part, by the modified expression of those genes.expression of Hsp27, S100A4, p21, IL-8 and the increased expression of IGFBP-2 was also observed in vivo, in leukemic patients. Our results suggest that the favorable prognosis of PRAME could be mediated, at least in part, by the modified expression of those genes.

Document type Article de périodique (Journal article) – Article de recherche – In Vitro, Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2008
Language Anglais
Journal information "Leukemia and Lymphoma" - Vol. 49, no. 6, p. 1123-1131 (2008)
Peer reviewed yes
Publisher Informa Healthcare ((United Kingdom) London)
issn 1042-8194
e-issn 1029-2403
Publication status Publié
Affiliations UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation
UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - SSS/IONS - Institute of NeuroScience
UCL - SSS/IREC/CTMA - Centre de technologies moléculaires appliquées (plate-forme technologique)
UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique
UCL - (SLuc) Service d'urologie
UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
MESH Subject Tumor Markers, Biological - genetics - metabolism ; S100 Proteins - genetics - metabolism ; RNA, Small Interfering - pharmacology ; Prognosis ; Oligonucleotide Array Sequence Analysis ; Neoplasm Proteins - genetics - metabolism ; Leukemia, Myeloid, Acute - genetics - metabolism ; Interleukin-8 - genetics - metabolism ; Insulin-Like Growth Factor Binding Protein 2 - genetics - metabolism ; Humans ; Heat-Shock Proteins - genetics - metabolism ; HSP27 Heat-Shock Proteins ; Gene Expression Profiling ; Cyclin-Dependent Kinase Inhibitor p21 - genetics - metabolism ; Child ; Antigens, Neoplasm - chemistry - genetics - metabolism
Keywords PRAME ; leukemia ; prognosis ; cell death ; cell proliferation ; cell cycle and apoptosis changes ; neoplasia ; prognostication ; myeloid leukemias and dysplasias
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Bibliographic reference Tajeddine, Nicolas ; Louis, Magali ; Vermylen, Christiane ; Gala, Jean-Luc ; Tombal, Bertrand ; et. al. Tumor associated antigen PRAME is a marker of favorable prognosis in childhood acute myeloid leukemia patients and modifies the expression of S100A4, Hsp 27, p21, IL-8 and IGFBP-2 in vitro and in vivo. In: Leukemia and Lymphoma, Vol. 49, no. 6, p. 1123-1131 (2008)
Permanent URL http://hdl.handle.net/2078.1/12540