- Blood. 2002 Aug 15;100(4):1410-6.
- V(H) mutation status, CD38 expression
level, genomic aberrations, and survival in chronic lymphocytic leukemia.
Krober A, Seiler T, Benner A, Bullinger L, Bruckle E, Lichter P, Dohner H, Stilgenbauer S.
Abteilung Innere Medizin III, University of Ulm, Germany.
In chronic lymphocytic leukemia (CLL), biologic risk factors such as immunoglobulin
variable heavy chain gene (V(H)) mutation status, CD38 expression level, and genomic
aberrations have recently been identified, but the relative prognostic impact of the
individual parameters is unknown. In the current study, we analyzed V(H) mutation status
by polymerase chain reaction and sequencing (n = 300), genomic aberrations by fluorescence
in situ hybridization (+3q, 6q-, +8q, 11q-, +12q, 13q-, t(14q), 17p-) (n = 300), and CD38
expression by triple-color FACS (CD5, CD19, CD38) (n = 157) in a unicentric CLL cohort.
The prognostic influence of V(H) mutation rate and CD38 expression level was tested by
maximally selected log-rank statistics. A corrected P value (P(cor)) for a cutoff level
allowing the best separation of 2 subgroups with different survival probabilities was
identified at 97% V(H) homology (95% confidence interval [CI], 96%-98% homology, P(cor)
<.001) and at 7% CD38 expression (95% CI, 20%-71% expression, P(cor) =.02). In
univariate analyses, unmutated V(H) genes and high CD38 expression levels predicted for
shorter survival times. The overall incidence of genomic aberrations was similar in the
V(H) unmutated and V(H) mutated subgroups. High-risk genomic aberrations such as 17p- and
11q- occurred almost exclusively in the V(H) unmutated subgroup, whereas favorable
aberrations such as 13q- and 13q- as single abnormalities were overrepresented in the V(H)
mutated subgroup. In multivariate analysis, unmutated V(H), 17p deletion, 11q deletion,
age, WBC, and LDH were identified as independent prognostic factors, indicating a
complementary role of V(H) mutation status and genomic aberrations to predict outcome in
CLL.
PMID: 12149225 [PubMed - indexed for MEDLINE]