title: CD38 expression level and pattern of expression remains a reliable and robust marker of progressive disease in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) follows a variable clinical course which is difficult to predict at diagnosis. We assessed somatic mutation (SHM) status, CD38 and ZAP-70 expression in 87 patients (49 male, 38 female) with stage A CLL and known cytogenetic profile to compare their role in predicting disease progression, which was assessed by the treatment free interval (TFI) from diagnosis. Sixty (69%) patients were SHM+, 24 (28%) were CD38+ and ten (12%) were ZAP-70+. The median TFI for: (i) SHM + versus SHM- patients was 124 versus 26 months; hazard ratio (HR) = 3.6 [95% confidence interval (CI) = 1.8 - 7.3; P = 0.001]: (ii) CD38- versus CD38+ patients was 120 versus 34 months; HR = 2.4 (95% CI = 1.4 - 5.3; P = 0.02); and (iii) ZAP70- versus ZAP70+ was 120 versus 16 months; HR = 3.4 (95% CI = 1.4 - 8.7; P = 0.01). SHM status and CD38 retained prognostic significance on multivariate analysis whereas ZAP-70 did not. We conclude that ZAP-70 analysis does not provide additional prognostic information in this group of patients.
authors.affiliation: Department of Haematology and Durkan Laboratories, Institute of Molecular Medicine, Trinity College and St James Hospital, Dublin, Ireland.
authors.forename: Amjad
authors.initials: A
authors.lastname: Hayat
authors.forename: David
authors.initials: D
authors.lastname: O'Brien
authors.forename: Paul
authors.initials: P
authors.lastname: O'Rourke
authors.forename: Siobhan
authors.initials: S
authors.lastname: McGuckin
authors.forename: Tony
authors.initials: T
authors.lastname: Fitzgerald
authors.forename: Eibhlin
authors.initials: E
authors.lastname: Conneally
authors.forename: Paul V
authors.initials: PV
authors.lastname: Browne
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McCann
authors.forename: Mark P
authors.initials: MP
authors.lastname: Lawler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Vandenberghe
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D015996:Survival Rate; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1