Genomic imbalances associated with secondary acute leukemias in Hodgkin lymphoma
2007; Elsevier BV; Linguagem: Inglês
10.3892/or.18.6.1427
ISSN1791-2431
AutoresGianluca Brusa, Elisa Zuffa, Claudia Maria Hattinger, Massimo Serra, Daniel Remondini, Gastone Castellani, Simona Righi, Cristina Campidelli, Stefano Pileri, Pier Luigi Zinzani, Annalisa Gabriele, Manuela Mancini, Patrizia Corrado, Elena Barbieri, Maria Alessandra Santucci,
Tópico(s)Epigenetics and DNA Methylation
ResumoSecondary tumors and leukemias are major complications in Hodgkin lymphoma (HL). They likely arise from clonal selection of cells that have accumulated genomic lesions induced by chemo- and radiotherapy and may be further promoted by the loss of DNA repair and/or other pathways ensuring the fidelity of replicated DNA. To distinguish genomic imbalances associated with the development of acute myeloid leukemia (AML) in HL we used an array-based comparative genomic hybridization (aCGH) strategy on whole lymph node biopsies of HL patient. Genomic imbalances (amplifications and deletions) associated with AML outcome in 3 classic HL patients, at clinical diagnosis they exhibited a discrete individual variability. Three amplifications and 5 deletions were shared by all 3 patients. They involved AFM137XA11, a 9p11.2 pericentric region; FGFR1, the FGF receptor most frequently translocated in AML; PPARBP, a co-activator of nuclear receptors RARalpha, RXR and TRbeta1; AFM217YD10, a 17q25 telomeric region; FGR, an SRC2 kinase involved in cytokine production by NK and CD4+ NKT cells; GATA3, a Th2-specific transcription factor; TOP1, involved in DNA recombination and repair; WT1, a transcription factor involved in CD8+ T cell response against leukaemic blasts. Immunohistochemistry confirmed aCGH results and distinguished the distribution of either amplified or deleted gene products in neoplastic Reed Sternberg (RS) cells and non-neoplastic lymph node components.
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