title: Protein profiles distinguish stable and progressive chronic lymphocytic leukemia.
abstract: Patients with a stable chronic lymphocytic leukemia (CLL) double their blood lymphocyte count in >5 years, but may develop progressive disease with lymphocytes doubling in <12 months. To identify a protein signature for progressive CLL, whole cell extracts of peripheral blood mononuclear cells from patients with CLL (n=27) were screened using iTRAQ (isobaric tags for relative and absolute quantification) analysis. A total of 84 differentially abundant proteins were identified from patients with stable and progressive CLL. Subsequently, 32 of these proteins were quantified by SRM (selected reaction monitoring) using extracts of purified CD19+ CLL cells from patients (n=50). Hierarchical clustering of these protein profiles showed two clusters of patients that correlated with progressive and stable CLL, providing signatures that should be useful for triaging patients. Some of the proteins in the progressive cluster have not been linked with CLL, for example, glutamate dehydrogenase 1 and transcription intermediary factor 1-beta.
authors.affiliation: a School of Molecular Bioscience, University of Sydney , Sydney , NSW , Australia ;
authors.forename: Pauline Y
authors.initials: PY
authors.lastname: Huang
authors.affiliation: a School of Molecular Bioscience, University of Sydney , Sydney , NSW , Australia ;
authors.forename: Swetlana
authors.initials: S
authors.lastname: Mactier
authors.affiliation: a School of Molecular Bioscience, University of Sydney , Sydney , NSW , Australia ;
authors.forename: Natalie
authors.initials: N
authors.lastname: Armacki
authors.affiliation: b Northern Blood Research Centre, Kolling Institute of Medical Research, Royal North Shore Hospital , St. Leonards , NSW , Australia ;
authors.forename: O
authors.initials: O
authors.lastname: Giles Best
authors.affiliation: a School of Molecular Bioscience, University of Sydney , Sydney , NSW , Australia ;
authors.forename: Larissa
authors.initials: L
authors.lastname: Belov
authors.affiliation: a School of Molecular Bioscience, University of Sydney , Sydney , NSW , Australia ;
authors.forename: Kimberley L
authors.initials: KL
authors.lastname: Kaufman
authors.affiliation: c Australian Proteome Analysis Facility, Macquarie University , North Ryde , NSW , Australia.
authors.forename: Dana
authors.initials: D
authors.lastname: Pascovici
authors.affiliation: b Northern Blood Research Centre, Kolling Institute of Medical Research, Royal North Shore Hospital , St. Leonards , NSW , Australia ;
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Mulligan
authors.affiliation: a School of Molecular Bioscience, University of Sydney , Sydney , NSW , Australia ;
authors.forename: Richard I
authors.initials: RI
authors.lastname: Christopherson
mesh_terms: D014408:Biomarkers, Tumor; D002853:Chromatography, Liquid; D016000:Cluster Analysis; D018450:Disease Progression; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D020543:Proteome; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome
keywords: Chronic lymphocytic leukemia; iTRAQ; mass spectrometry; prognostic markers; proteomics; selected reaction monitoring