Clonal diversity predicts adverse outcome in chronic lymphocytic leukemia

Genomic analyses of chronic lymphocytic leukemia (CLL) identified somatic mutations and associations of clonal diversity with adverse outcomes. Clonal evolution likely has therapeutic implications but its dynamic is less well studied. We studied clonal composition and prognostic value of seven recur...

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Bibliographic Details
Published in:Leukemia 2019-02, Vol.33 (2), p.390-402
Main Authors: Leeksma, Alexander C, Taylor, Justin, Wu, Bian, Gardner, Jeffrey R, He, Jie, Nahas, Michelle, Gonen, Mithat, Alemayehu, Wendimagegn G, Te Raa, Doreen, Walther, Tatjana, Hüllein, Jennifer, Dietrich, Sascha, Claus, Rainer, de Boer, Fransien, de Heer, Koen, Dubois, Julie, Dampmann, Maria, Dürig, Jan, van Oers, Marinus H J, Geisler, Christian H, Eldering, Eric, Levine, Ross L, Miller, Vincent, Mughal, Tariq, Lamanna, Nicole, Frattini, Mark G, Heaney, Mark L, Zelenetz, Andrew, Zenz, Thorsten, Abdel-Wahab, Omar, Kater, Arnon P
Format: Article
Language:English
Subjects:
Analysis
Biomarkers, Tumor - genetics
Care and treatment
Cdc4 protein
Chronic lymphocytic leukemia
Clinical Trials as Topic
Clonal Evolution
Development and progression
Disease Progression
Evolution
FOXO3 protein
Gene expression
Gene mutation
Gene sequencing
Genes
Genetic aspects
Genomic analysis
Health aspects
High-Throughput Nucleotide Sequencing
Humans
Kinases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - mortality
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Lymphatic leukemia
Lymphocytic leukemia
MAP kinase
Medical research
Medical schools
Mutation
MyD88 protein
Next-generation sequencing
p53 Protein
Patients
Prognosis
Survival Rate
Tumor proteins
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Description
Summary:Genomic analyses of chronic lymphocytic leukemia (CLL) identified somatic mutations and associations of clonal diversity with adverse outcomes. Clonal evolution likely has therapeutic implications but its dynamic is less well studied. We studied clonal composition and prognostic value of seven recurrently mutated driver genes using targeted next-generation sequencing in 643 CLL patients and found higher frequencies of mutations in TP53 (35 vs. 12%, p 
ISSN:0887-6924
1476-5551
DOI:10.1038/s41375-018-0215-9