Genome-wide promoter methylation of hairy cell leukemia

Alberto J. Arribas, Andrea Rinaldi, Giorgia Chiodin, Ivo Kwee, Afua Adjeiwaa Mensah, Luciano Cascione, Davide Rossi, Meena Kanduri, Richard Rosenquist, Emanuele Zucca, Peter W. Johnson, Gianluca Gaidano, Christopher C. Oakes, Francesco Bertoni, Francesco Forconi

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Classic hairy cell leukemia (HCL) is a tumor of mature clonal B cells with unique genetic, morphologic, and phenotypic features. DNA methylation profiling has provided a new tier of investigation to gain insight into the origin and behavior of B-cell malignancies; however, the methylation profile of HCL has not been specifically investigated. DNA methylation profiling was analyzed with the Infinium HumanMethylation27 array in 41 mature B-cell tumors, including 11 HCL, 7 splenic marginal zone lymphomas (SMZLs), and chronic lymphocytic leukemia with an unmutated (n 5 7) or mutated (n 5 6) immunoglobulin gene heavy chain variable (IGHV) region or using IGHV3-21 (n 5 10). Methylation profiles of nontumor B-cell subsets and gene expression profiling data were obtained from public databases. HCL had a methylation signature distinct from each B-cell tumor entity, including the closest entity, SMZL. Comparison with normal B-cell subsets revealed the strongest similarity with postgerminal center (GC) B cells and a clear separation from pre-GC and GC cellular programs. Comparison of the integrated analysis with post-GC B cells revealed significant hypomethylation and overexpression of BCR–TLR–NF-kB and BRAF-MAPK signaling pathways and cell adhesion, as well as hypermethylation and underexpression of cell-differentiation markers and methylated genes in cancer, suggesting regulation of the transformed hairy cells through specific components of the B-cell receptor and the BRAF signaling pathways. Our data identify a specific methylation profile of HCL, which may help to distinguish it from other mature B-cell tumors.

Lingua originaleInglese
pagine (da-a)384-396
Numero di pagine13
RivistaBlood advances
Volume3
Numero di pubblicazione3
DOI
Stato di pubblicazionePubblicato - 12 feb 2019

Fingerprint

Entra nei temi di ricerca di 'Genome-wide promoter methylation of hairy cell leukemia'. Insieme formano una fingerprint unica.

Cita questo