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Can Proteomic Profiling Improve Therapeutic Outcomes for Patients With CLL?

By: Joshua D. Madera, MS
Posted: Tuesday, May 24, 2022

The use of proteomic analysis in patients with chronic lymphocytic leukemia (CLL) may improve disease classification and provide useful clinical information for patient management, according to a study published in Blood Cancer Journal. Furthermore, proteomics may play an essential role in identifying therapeutic strategies and potential therapeutic targets, explained Steven M. Kornblau, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

“Proteomic classification supersedes clinical-based staging and confirms the additive prognostic importance of protein signature classification to existing classifiers,” commented the study investigators.

From 2005 to 2019, a total of 871 protein samples were collected from patients with CLL and related mature small B-cell neoplasms and leukemias. Then, 384 total and post-translationally modified proteins were analyzed for protein expression. Proteomic profiles were created for each of the 871 protein samples using a reverse phase protein array.

Via proteomic analysis, six recurrent signatures indicative of survival and the time to first or second treatment were identified. These signatures were highly prognostic when grouped systemically in signatures for individual proteins and when grouped into 40 functionally protein-related groups. Furthermore, proteomic signatures were significantly better than Rai staging and immunoglobulin heavy variable mutation status, as demonstrated by an improved prognostic response to both older CLL therapies and modern Bruton’s tyrosine kinase inhibitors, the authors found. Moreover, the use of proteomic signatures and the 40 functionally related groups aided in the identification of novel therapeutic targets for this patient population. Optimal candidates were also identified for early intervention versus watchful waiting.

Disclosure: For full disclosures of the study authors, visit nature.com.


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