title: Percentage of smudge cells determined on routine blood smears is a novel prognostic factor in chronic lymphocytic leukemia.
abstract: Recently developed molecular prognostic tests in patients with early Binet stage chronic lymphocytic leukemia (B-CLL) are costly and often require a high level of technologic expertise. Recent data give evidence for the prognostic relevance of the percentage of smudge cells in B-CLL. In our study we analysed the prognostic potential of this novel marker in a cohort of 100 CLL patients. The percentage of smudge cells ranged from 0% to 70% (median 21%). Patients with <or=20% smudge cells (according to ROC analysis) had a significantly shorter time to first treatment and overall survival than patients with >20% smudge cells. Multivariate Cox regression analysis identified percentages of smudge cells, stage according to Binet and CD38 expression as independent prognostic markers. The percentage of smudge cells was significantly lower in CD38+, ZAP-70+ and unmutated IgVH patients. Combined analysis of smudge cell percentages with CD38 expression provided complementary prognostic information identifying three patient subgroups with good, intermediate and poor prognosis. Comparing gene expression profiles in a subset of 12 patients we identified eight differentially expressed genes in groups with high vs. low percentage of smudge cells suggesting a role of these differentially expressed genes, especially for Tribbles homolog 2 (Trib2), in the disease progression of high risk CLL patients. In conclusion, our data confirm previous studies showing that the simple and inexpensive microscopic detection of smudge cells on blood smears prepared for routine diagnostic purposes is a novel independent factor predicting overall survival in CLL.
authors.affiliation: Department of Hematology, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Johansson
authors.forename: L
authors.initials: L
authors.lastname: Eisele
authors.forename: L
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: L
authors.initials: L
authors.lastname: Sellmann
authors.forename: U
authors.initials: U
authors.lastname: Dührsen
authors.forename: J
authors.initials: J
authors.lastname: Dürig
authors.forename: H
authors.initials: H
authors.lastname: Nückel
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000648:ultrastructure*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016923:Cell Death; D002869:Chromosome Aberrations; D003955:Diagnostic Tests, Routine; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D014746:Vimentin / Q000097:blood / Q000502:physiology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000097:blood
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D014746:Vimentin; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1