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Genome-wide promoter methylation of hairy cell leukemia

Genome-wide promoter methylation of hairy cell leukemia
Genome-wide promoter methylation of hairy cell leukemia

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 = 7) or mutated (n = 6) immunoglobulin gene heavy chain variable (IGHV) region or using IGHV3-21 (n = 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-κB 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.

2473-9529
384-396
Arribas, Alberto J.
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Rinaldi, Andrea
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Chiodin, Giorgia
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Kwee, Ivo
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Mensah, Afua Adjeiwaa
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Cascione, Luciano
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Rossi, Davide
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Kanduri, Meena
174e044e-0b44-439e-b590-df663f2f4b5b
Rosenquist, Richard
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Zucca, Emanuele
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Johnson, Peter W.
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Gaidano, Gianluca
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Oakes, Christopher C.
a3d8d8e6-dc0e-4dde-87a7-2723623302cf
Bertoni, Francesco
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Forconi, Francesco
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Arribas, Alberto J.
cd8e70cb-e804-4050-906f-ab04005ee602
Rinaldi, Andrea
ae4d2559-25e9-47b8-8c77-308f6cb2a5c4
Chiodin, Giorgia
4b3e9525-b377-4d16-b69a-e05d2e7854fe
Kwee, Ivo
0926a658-8296-4ba4-9a70-abcf8a1aad96
Mensah, Afua Adjeiwaa
a67cf26b-4e10-4ef3-83fd-4cd25a8d5242
Cascione, Luciano
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Rossi, Davide
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Kanduri, Meena
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Rosenquist, Richard
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Zucca, Emanuele
40bd5950-d74e-4169-a2ea-0bfc1058058e
Johnson, Peter W.
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Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Oakes, Christopher C.
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Bertoni, Francesco
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Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8

Arribas, Alberto J., Rinaldi, Andrea, Chiodin, Giorgia, Kwee, Ivo, Mensah, Afua Adjeiwaa, Cascione, Luciano, Rossi, Davide, Kanduri, Meena, Rosenquist, Richard, Zucca, Emanuele, Johnson, Peter W., Gaidano, Gianluca, Oakes, Christopher C., Bertoni, Francesco and Forconi, Francesco (2019) Genome-wide promoter methylation of hairy cell leukemia. Blood Advances, 3 (3), 384-396. (doi:10.1182/bloodadvances.2018024059).

Record type: Article

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 = 7) or mutated (n = 6) immunoglobulin gene heavy chain variable (IGHV) region or using IGHV3-21 (n = 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-κB 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.

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Accepted/In Press date: 2 January 2019
e-pub ahead of print date: 5 February 2019
Published date: 12 February 2019

Identifiers

Local EPrints ID: 428564
URI: http://eprints.soton.ac.uk/id/eprint/428564
ISSN: 2473-9529
PURE UUID: 4ba92c16-fc81-41f1-972c-39c937a9db84
ORCID for Peter W. Johnson: ORCID iD orcid.org/0000-0003-2306-4974

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Date deposited: 01 Mar 2019 17:30
Last modified: 26 Nov 2021 02:41

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Contributors

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

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