TY - JOUR
T1 - Genome-wide promoter methylation of hairy cell leukemia
AU - Arribas, Alberto J.
AU - Rinaldi, Andrea
AU - Chiodin, Giorgia
AU - Kwee, Ivo
AU - Mensah, Afua Adjeiwaa
AU - Cascione, Luciano
AU - Rossi, Davide
AU - Kanduri, Meena
AU - Rosenquist, Richard
AU - Zucca, Emanuele
AU - Johnson, Peter W.
AU - Gaidano, Gianluca
AU - Oakes, Christopher C.
AU - Bertoni, Francesco
AU - Forconi, Francesco
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology
PY - 2019/2/12
Y1 - 2019/2/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85061117939
U2 - 10.1182/bloodadvances.2018024059
DO - 10.1182/bloodadvances.2018024059
M3 - Article
SN - 2473-9529
VL - 3
SP - 384
EP - 396
JO - Blood advances
JF - Blood advances
IS - 3
ER -
