In a paper published in Clinical Cancer Research, Ken He Young, MD, PhD, and Zijun Yidan Xu-Monette, PhD, explore the lymphoma clinical and biological features using next generation sequencing and biological technology in diffuse large B-cell lymphoma (DLBCL).
Genetic subtyping based on signatures of genetic driver alterations has been proposed recently to classify DLBCL, the most common aggressive B-cell lymphoma in the world. In a recent paper published in Clinical Cancer Research, Dr. Ken H. Young’s group in the Department of Pathology demonstrated the prognostic values of genetic subtypes, MYC/BCL2 double protein expression, and the tumor immune microenvironment (TME) in a large cohort of DLBCL. In this study, Dr. Xu-Monette and other authors uncovered independent and additive prognostic effects of genetic and phenotypic biomarkers in DLBCL. They first revealed phenotypic heterogeneity within genetic subtypes, and suggested that cost-effective immunohistochemistry-based biomarkers have clinical utility in the genomic era. They subsequently showed that genetic subtypes affected the prognostic significance of immunophenotypic biomarkers (TME and MYC/BCL2), and that MYC/BCL2 double-high expressors could be further stratified by KMT2D mutations, which suggested a role of genetic alterations in defining prognosis and potential of novel therapies. The authors finally showed the prognostic impacts of TME in MYC/BCL2 double expressors, and that although MYC/BCL2 and high Ki-67 expression were associated with lower T-cell infiltration, the prognostic effects of MYC/BCL2 and immune signatures were independent. These findings are important for understanding the prognostic determinants in DLBCL and improving DLBCL classification and precision medicine in clinic applications. The study was supported by the National Cancer Institute, National Institutes of Health and Duke Cancer Institute.
Young is a Professor of Pathology, member of the Duke Cancer Institute, and Director of a Hematopathology Division that provides diagnostic consultation services and relevant specialized testing for patients with various types of acute and chronic leukemia, lymphoma and benign hematologic disorders.
Xu-Monette is an Assistant Professor of Pathology and member of the Duke Cancer Institute, Her research efforts have been focused on identifying prognostic and therapeutic biomarkers in B-cell lymphoma.
