Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance.

Autor: Bock AM; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA.; Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA., Wenzl K; Translational Medicine Hematology, Bristol Myers Squibb, Summit, New Jersey, USA., Novak JP; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Stokes ME; Informatics and Predictive Sciences, Bristol Myers Squibb, Summit, New Jersey, USA., Hopper MA; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Krull JE; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Dropik AR; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Sarangi V; Department of Quantitative Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Ortiz M; Informatics and Predictive Sciences, Bristol Myers Squibb, Seville, Spain., Stong N; Informatics and Predictive Sciences, Bristol Myers Squibb, Summit, New Jersey, USA., Huang CC; Translational Medicine Hematology, Bristol Myers Squibb, Summit, New Jersey, USA., Maurer MJ; Informatics and Predictive Sciences, Bristol Myers Squibb, Summit, New Jersey, USA., King RL; Division of Hematopathology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Farooq U; Division of Hematology, University of Iowa, Iowa City, Iowa, USA., Wang Y; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Witzig TE; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Ansell SM; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Habermann TM; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Cerhan JR; Informatics and Predictive Sciences, Bristol Myers Squibb, Summit, New Jersey, USA., Gandhi AK; Translational Medicine Hematology, Bristol Myers Squibb, Summit, New Jersey, USA., Nowakowski G; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Novak AJ; Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA.
Jazyk: angličtina
Zdroj: Hematological oncology [Hematol Oncol] 2025 Jan; Vol. 43 (1), pp. e70006.
DOI: 10.1002/hon.70006
Abstrakt: Diffuse large B-cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non-PTR DLBCL. We found a significant increase in the frequency of TP53 (34% vs. 15%, p = 0.005) and ARID1A mutations (21% vs. 7%, p = 0.007) in PTR cases, with pathway analysis further demonstrating a downregulation of TP53 and an increase in chromatin modifying pathways. These results suggest that TP53 and ARID1A may be key mediators of PTR and important pathways contributing to the poor outcomes. We found that the current molecular classifiers were unable to identify PTR cases at diagnosis. However, our newly identified high-risk signature identified 46% of PTR cases at diagnosis. Overall, these results contribute to our understanding of the genomic landscape of patients with primary treatment resistance.
(© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: