Genomic imbalances associated with secondary acute leukemias in Hodgkin lymphoma.
Secondary 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.
Brusa
Gianluca
G
Istituto di Ematologia e Oncologia Medica Lorenzo e Ariosto Seràgnoli, Università di Bologna - Medical School, 40138 Bologna, Italy. gbrusa@alma.unibo.it
Zuffa
Elisa
E
Hattinger
Claudia Maria
CM
Serra
Massimo
M
Remondini
Daniel
D
Castellani
Gastone
G
Righi
Simona
S
Campidelli
Cristina
C
Pileri
Stefano
S
Zinzani
Pier Luigi
PL
Gabriele
Annalisa
A
Mancini
Manuela
M
Corrado
Patrizia
P
Barbieri
Enza
E
Santucci
Maria Alessandra
MA
D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004260:DNA Repair; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D017353:Gene Deletion; D042822:Genomic Instability; D006689:Hodgkin Disease / Q000150:complications / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000071447:N-Myc Proto-Oncogene Protein; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins