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Study Suggests Epigenetic Therapy May Help Subgroup of Patients With Marginal Zone Lymphoma

Alison Rodriguez
Epigenetic drug therapy should be explored for certain patients with marginal zone lymphoma, according to a recent study.
Mucosa-associated lymphoid tissue (MALT) lymphomas are characterized by lesions affecting chromatin remodeling and the methylation and transcriptome data suggest epigenetic drug therapy should be explored for certain patients with marginal zone lymphoma (MZL), according to a report published by Haematologica.

The researchers investigated 72 cases of MALT lymphomas from different anatomic sites, including lungs (32%), ocular adnexa (28%), salivary glands (18%), thyroid (7%), stomach (5%), and other (10%) for DNA copy number variations (CNVs) and for the mutational status of previously reported mutated genes in B cell lymphomas.

“MALT lymphoma is the most common type of marginal zone lymphoma (MZL) representing 5% to 8% of all B-cell lymphomas and occurs at diverse anatomic sites with site-specific clinical and biological differences,” explained the authors. “Unique among the three MZL (extranodal MZL of MALT type, splenic MZL, and nodal MZL), MALT lymphomas have recurrent chromosomal translocations with the BIRC3-MALT1 being the most frequent event observed in 15-40% of cases especially those occurring in the lung and stomach.”

The case analyses revealed an average of 3 mutated genes per patient—70 patients had at least 1 event (mutations or genomic alteration) and the mutations were detected in 90 genes in at least 1 case. According to the results, there was no association between mutational status and clinical stage.

The researchers suggested that the presence of TET2 mutations may be associated with a higher response to demethylating agents in acute myeloid leukemia; since these agents can revert the methylator phenotype, epigenetic therapy may be effective in patients with TET2 mutated MALT lymphomas.

“As the gene expression signatures associated with the presence of the BIRC3-MALT fusion and with trisomy 3 appeared negatively correlated with the transcriptome changes induced by other epigenetic agents, there might be the potential to study BET inhibitors and HDAC inhibitors in these patients,” concluded the authors. “MALT lymphomas are characterized by frequent lesions affecting chromatin remodeling, BCR/NF-κB and NOTCH pathways. Lymphomas from different anatomic sites exhibit a different spectrum of genetic lesions.”

Reference

Cascione L, Rinaldi A, Bruscaggin A, et al. Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses [published online April 24, 2019]. Haematologica. Doi:10.3324/haematol.2018.214957

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