IgM-MM is predominantly a pre-germinal center disorder and has a distinct genomic and transcriptomic signature from WM.

Autor:	Bazarbachi AH; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.; Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, New York, NY., Avet-Loiseau H; University Cancer Center of Toulouse, Institut National de la Santé, Toulouse, France., Szalat R; Department of Hematology and Medical Oncology, Boston University Medical Center, Boston, MA., Samur AA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA., Hunter Z; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Shammas M; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Corre J; University Cancer Center of Toulouse, Institut National de la Santé, Toulouse, France., Fulciniti M; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Anderson KC; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Parmigiani G; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA., Treon SP; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Mohty M; Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, INSERM UMRs 938, Université Sorbonne, Paris, France; and., Munshi NC; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.; VA Boston Healthcare System, Boston, MA., Samur MK; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 Nov 18; Vol. 138 (20), pp. 1980-1985.
DOI:	10.1182/blood.2021011452
Abstrakt:	Immunoglobulin M (IgM) multiple myeloma (MM) is a rare disease subgroup. Its differentiation from other IgM-producing gammopathies such as Waldenström macroglobulinemia (WM) has not been well characterized but is essential for proper risk assessment and treatment. In this study, we investigated genomic and transcriptomic characteristics of IgM-MM samples using whole-genome and transcriptome sequencing to identify differentiating characteristics from non-IgM-MM and WM. Our results suggest that IgM-MM shares most of its defining structural variants and gene-expression profiling with MM, but has some key characteristics, including t(11;14) translocation, chromosome 6 and 13 deletion as well as distinct molecular and transcription-factor signatures. Furthermore, IgM-MM translocations were predominantly characterized by VHDHJH recombination-induced breakpoints, as opposed to the usual class-switching region breakpoints; coupled with its lack of class switching, these data favor a pre-germinal center origin. Finally, we found elevated expression of clinically relevant targets, including CD20 and Bruton tyrosine kinase, as well as high BCL2/BCL2L1 ratio in IgM-MM, providing potential for targeted therapeutics. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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