Perfil mutacional de linfomas b con diferenciación plasmocelular

Abstract

The aim of this research, was to describe the mutational profile of a series of B cell lymphoma with plasma cell differentiation, including lymphoplasmacytic B cell lymphoma and plasmablastic lymphoma. The secondary aims were: the study of the relationship between the mutational profile and the phenotype and the characterization of the tumor microenvironment as well as the expression immune checkpoint related proteins in cases of plasmablastic lymphoma. Samples of lymphoplasmacytic lymphoma, IgM monoclonal gammapathy of uncertain significance and plasmablastic lymphoma were subjected to a comprehensive analysis including immunohistochemistry, in situ hybridization, targeted NGS sequencing, Sanger sequencing and Allele specific Quantitative PCR. A detailed characterization of the immune populations as well as the expression of immune checkpoint markers was done in plasmablastic lymphoma cases. Our results show that lymphoplasmacytic lymphoma is characterized by a simple mutational profile, with a recurrent mutation in MYD88pL265P and occasional somatic mutations in CXCR4, KMT2D, PRDM1/Blimp1, MYC and ID3. The mutational profile of plasmablastic lymphoma is heterogeneous and associated with EBV infection. Genetic lesions in MYC, STAT3 and PRDM1/Blimp1 are more frequent in EBV positive tumors. In some cases, MAPK pathway mutations such as BRAF are detected. Both MYC rearrangements and STAT3 SH2 mutations lead to overexpression of MYC and PhosphoSTAT3. An enrichment in TAM and PD1 reactive T lymphocytes is found in the microenvironment of plasmablastic lymphoma. Targeted NGS methods are suitable for the molecular diagnosis of B lymphomas. The identification of characteristic recurrent mutations in JAK/STAT and MAPK pathway in plasmablastic lymphomas may offer new therapeutic options for these lymphomas.