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| Item Type: | Article |
|---|---|
| Title: | Comparative DNA methylation profiling of human and murine ALK‐positive B‐cell neoplasms |
| Creators: |
Glaser, Selina  ORCID: https://orcid.org/0009-0008-2923-1829, Wagener, Rabea, Harkins, Shannon K., Voena, Claudia, Bens, Susanne, Klapper, Wolfram ORCID: https://orcid.org/0000-0001-7208-4117, Laurent, Camille, Mathas, Sephan ORCID: https://orcid.org/0000-0001-9626-1413, Ren, Meiqi, Sander, Sandrine ORCID: https://orcid.org/0000-0003-4645-3366, Schnaudt‐Mastrangelo, Charlotte, Wößmann, Wilhelm ORCID: https://orcid.org/0000-0002-6315-0888, Xerri, Luc, Ammerpohl, Ole, Zelenetz, Andrew D., Louissaint, Abner, Chiarle, Roberto and Siebert, Reiner
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| Abstract: | Structural genomic variants leading to anaplastic lymphoma kinase (ALK) gene fusions and aberrant expression of the ALK tyrosine kinase are the hallmark of subtypes of T- and B-lineage neoplasms, namely ALK-positive anaplastic large lymphoma (ALCL) and ALK-positive large B-cell lymphoma (LBCL). The latter is a rare aggressive lymphoma, which has been initially identified as a variant of diffuse LBCL (DLBCL) with plasmablastic features. Here, we performed comparative DNA methylation profiling of human and murine ALK-positive B-cell neoplasms. Array-based DNA methylation data from ALK-positive LBCL samples of eight patients were compared to that of DLBCL (n = 75), multiple myeloma (MM, n = 24), ALK-positive ALCL (n = 12) and normal B-cell populations (n = 93). ALK-positive LBCLs share a distinct DNA methylation signature similar to that of MM, characterized by lower global DNA methylation levels compared to DLBCLs and normal B-cell populations. DNA methylation alterations in ALK-positive LBCL were predominantly located in heterochromatic and polycomb-repressed regions. The epigenetic age and relative proliferative history of ALK-positive LBCL were intermediate between MM and DLBCL. B-cell neoplasms in NPM::ALK transgenic mice showed a similar hypomethylated signature when compared to normal murine B cells. Cross-species comparison indicated conservation of chromatin states and pathways affected by hypomethylation. Together, the findings suggest that in line with their phenotypical appearance human and murine ALK-positive B-cell lymphomas share an epigenetic profile more closely resembling that of plasma cell neoplasias than that of DLBCLs. |
| Keywords: | ALK-Positive LBCLs, DNA Methylation, Transgenic Mouse Model, Animals, Mice |
| Source: | Genes Chromosomes & Cancer |
| ISSN: | 1045-2257 |
| Publisher: | Wiley |
| Volume: | 64 |
| Number: | 7 |
| Page Range: | e70060 |
| Date: | July 2025 |
| Official Publication: | https://doi.org/10.1002/gcc.70060 |
| PubMed: | View item in PubMed |
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