NeoTYPE® CLL Profile

The clinical course of chronic lymphocytic leukemia (CLL) is heterogenous, and it ranges from very indolent with a nearly normal life expectancy to rapidly progressive leading to early death. Genomic alterations in the TP53, BIRC3, NOTCH1, and SFB31 genes, unmutated IgVH and 17p deletion by FISH are associated with adverse outcomes, and their presence or absence can improve risk stratification and treatment selection beyond clinical staging and other prognostic biomarkers. However, the most powerful biomarkers are IgVH mutation status (available as optional add-on) and 17p deletion as determined by FISH.

SF3B1 mutations occur in 10-15% of CLL patients and serve as independent predictors of shortened time to treatment and poorer overall survival in CLL. NOTCH1 mutations occur in a similar proportion of CLL patients and are associated with poor prognosis, comparable to TP53 abnormalities. Genomic alterations in the ATM gene, which is located on 11q22-q23, are also associated with an adverse outcome, particularly when both ATM mutation and 11q deletion are present.

Mutations in CARD11, CD79B, CXCR4 and MYD88 are associated with primary (initial) susceptibility or resistance to BTK (Bruton tyrosine kinase) inhibitors in certain B-cell neoplasms. Mutations in MYD88 and CD79B are associated with inhibitor sensitivity, and mutations in CARD11 and CXCR4 are associated with primary resistance. Mutations in BTK and PLCG2 are associated with acquired ibrutinib resistance in patients with B-cell neoplasms who have relapsed and/or show acquired (secondary) resistance after an initial response to BTK (Bruton tyrosine kinase) inhibitors. Acquisition of the G101V mutation in the BCL2 gene may associate with resistance to venetoclax in CLL patients.