Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia.
Recent reports suggest that the expression of germline (GL) Ig variable region heavy-chain genes (VH) is a negative prognostic factor for B-cell chronic lymphocytic leukaemia (B-CLL) patients and that CLL B-cell CD38 expression may be a surrogate marker of Ig VH gene status. Currently, however, the usefulness of this surrogate marker is controversial. Therefore, our goal was to study the ability of CD38 to act as a surrogate marker for Ig VH somatic mutation (SM), and to identify differences in overall survival (OS), progression-free survival (PFS) and response in B-CLL patients based on these two markers. We first assessed the relationship between CD38 expression and Ig VH status on 131 B-CLL patients, including 66 patients enrolled in three North Central Cancer Treatment Group Trials. Although the mean percentages of CD38+ clonal B cells were significantly higher for patients classified as GL versus SM, CD38 was not a reliable marker for clonal B-cell SM. Overall, GL patients exhibited significantly shorter OS and PFS times than SM patients. Despite the inability of clonal B-cell CD38 expression to predict Ig VH mutation status, patients with < or =30% CD38+ cells did have shorter PFS and OS times than did CLL patients with < 30% CD38+ cells. Thus, the relationship between CD38 expression and Ig VH mutation status in B-CLL is not straightforward. Nevertheless, analysis in a co-operative group clinical trial setting suggests that both B-cell markers alone or in combination may have clinical usefulness. These data strongly encourage the study of these biological markers as they relate to disease heterogeneity in B-CLL.
Jelinek
D F
DF
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. jelinek.diane@mayo.edu
Tschumper
R C
RC
Geyer
S M
SM
Bone
N D
ND
Dewald
G W
GW
Hanson
C A
CA
Stenson
M J
MJ
Witzig
T E
TE
Tefferi
A
A
Kay
N E
NE
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005803:Genes, Immunoglobulin; D005819:Genetic Markers; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis*; D016016:Proportional Hazards Models; D012306:Risk; D027041:Somatic Hypermutation, Immunoglobulin; D018709:Statistics, Nonparametric; D015996:Survival Rate
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015415:Biomarkers; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1