Role of SIRT1, EZH2, and CXCR4 Pathways in Treating Diffuse Large B-Cell Lymphoma

By Patrick Daly - Last Updated: February 24, 2022

Robert E. Brown, MD, and collaborating researchers from the University of Texas Health Science Center at Houston McGovern Medical School in Houston, used morphoproteomics, a holistic approach to characterizing diseased cells, to reveal commonalities in the biology of patients with diffuse large B-cell lymphoma (DLBCL). According to the researchers’ report, published in Annals of Clinical and Laboratory Science, their analysis suggested that the SIRT1 (silent mating type information regulation 2 homolog 1), EZH2 (enhancer of Zeste homolog 2), and CXCR4 (C-X-C chemokine receptor 4) pathways could be effective avenues to target the biology of DLBCL.

The investigators performed a morphoproteomics analysis on a tissue sample microarray from nine cases of classic DLBCL, including the use of “immunohistochemical probes” to detect SIRT1, EZH2, CXCR4, “and their cellular compartmentalization by bright field microscopy.”

According to the report, the researchers detected of SIRT1 and EZH2 expression in a majority of tumoral nuclei for eight and nine cases of DLBCL, respectively. Additionally, the expression of CXCR4 was seen in “the cytoplasmic and/or plasmalemmal compartment at >50% of the tumor cells in all nine cases of DLBCL,” they reported. The findings on SIRT1 and EZH2 expression in DLBCL were largely consistent with morphoproteomic findings in B-cell acute lymphoblastic leukemia (ALL), a concordance which had “pharmacogenomic and therapeutic implications,” according to the authors.

Overall, Dr. Brown and colleagues closed with the opinion that targeting SIRT1, EZH2, and CXCR4 pathways with “relatively non-toxic adjuvant therapeutic agents such as metformin, melatonin, curcumin, sulforaphane, vitamin D3, and plerixafor,” could be effective in the treatment of DLBCL.

Post Tags:DLBCL