title: Frequency and prognostic impact of the aberrant CD8 expression in 5,523 patients with chronic lymphocytic leukemia.
abstract: BACKGROUND
  In patients with chronic lymphocytic leukemia (CLL), aberrant expression of the T-lineage antigen CD8 was reported in low frequencies. The clinical impact of this phenomenon remains in discussion.
  
  
  METHODS
  We analyzed 5,523 patients with CLL (21-97 years) by multiparametric flow cytometry and performed fluorescence in situ hybridization (FISH), immunoglobulin heavy chain variable (IGHV) region mutational status analysis, and clinical outcome studies.
  
  
  RESULTS
  CD8 was positive in 61/5,523 (1.1%) patients. ZAP-70 expression amounted to a mean of 25.4% in CD8-positive vs. 28.2% in CD8-negative cases (n.s.), CD38 expression to a mean of 38.6% vs. 34.0% (n.s.). Cytogenetic alterations did not differ significantly [CD8-positive vs. CD8-negative: 13q deletion: 24/36 (66.7%) vs. 2,015/3,368 (59.8%); trisomy 12:7/35 (20.0%) vs. 487/3,357 (14.5%); 11q deletion: 6/35 (17.1%) vs. 360/3,354 (10.7%)]. A mutated IGHV status showed similar frequency in CD8-positive and CD8-negative cases (31/44; 70.5% vs. 1,700/2,816; 60.4%; n.s.). CD8-positive patients had a shorter median time to treatment compared with CD8-negative patients (12.0 vs. 77.1 months, P = 0.008). In univariable Cox analysis, CD8-positivity adversely influenced median TTT (P = 0.011). In multivariable analysis, the strongest parameters were hemoglobin level and mutated IGHV status (P < 0.001 for both) but CD8-positivity was still relevant (P = 0.074).
  
  
  CONCLUSIONS
  This study confirms that CD8 expression is a recurrent albeit rare phenomenon in patients with CLL and suggests that CD8 expression has an adverse prognostic impact. Therefore, CD8 expression should be further investigated for its potential to contribute to risk stratification in patients with CLL.
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany. wolfgang.kern@mll.com
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.forename: Frank
authors.initials: F
authors.lastname: Dicker
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016827:CD8 Antigens / Q000378:metabolism*; D002869:Chromosome Aberrations; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1