Proteogenomic subtyping of chronic lymphocytic leukemia identifies subgroups with contrasting clinical outcome and distinct ex-vivo drug response profile

ABSTRACT: We have performed a comprehensive proteomic analysis of clinical patient samples of chronic lymphocytic leukemia (CLL) alongside genome-, transcriptome- and ex-vivo drug response profiling. Trisomy 12 and IGHV mutation status had the strongest impact on the proteome and transcriptome; and SF3B1 mutations preferentially affected the proteome. Unsupervised clustering of the proteome data partitioned CLL patients into six protein based subgroups (PG) with contrasting clinical behavior. PG1-4 could be explained by the impact of trisomy 12 and IGHV mutation status on protein abundances and another subgroup (PG6), was enriched for TP53 mutations. In addition we uncovered a new subgroup (PG5) only detectable from the proteome, characterized by low expression of central B-cell receptor proteins, altered splicing, metabolic reprogramming and increased sensitivity to proteasomal inhibition.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, B-cell Chronic Lymphocytic Leukemia Cell

DISEASE(S): Chronic Lymphocytic Leukemia

SUBMITTER: Mattias Vesterlund  

LAB HEAD: Janne Lehtiö

PROVIDER: PXD017453 | Pride | 2024-06-21

REPOSITORIES: Pride