Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia

Autor: Frank Griesinger, Lorenz Trümper, Jan Dürig, Ludger Klein-Hitpass, Ulrich Dührsen, B Kulle, Detlef Haase, Ludger Sellmann, Roland Schroers
Rok vydání: 2005
Předmět:
Oncology
Male
Cancer Research
Chronic lymphocytic leukemia
Medizin
CD38
0302 clinical medicine
immune system diseases
hemic and lymphatic diseases
In Situ Hybridization
Fluorescence
Oligonucleotide Array Sequence Analysis
Regulation of gene expression
Aged
80 and over
0303 health sciences
Hematology
Membrane Glycoproteins
ZAP-70 Protein-Tyrosine Kinase
biology
Gene Expression Regulation
Leukemic
hemic and immune systems
Middle Aged
Protein-Tyrosine Kinases
Leukemia
030220 oncology & carcinogenesis
Disease Progression
Female
Antibody
Immunoglobulin Heavy Chains
Adult
medicine.medical_specialty
chemical and pharmacologic phenomena
Gene Expression Regulation
Enzymologic
03 medical and health sciences
Antigens
CD
Predictive Value of Tests
Internal medicine
medicine
Humans
ADP-ribosyl Cyclase
Survival analysis
030304 developmental biology
Aged
Chromosome Aberrations
Gene Expression Profiling
Reproducibility of Results
medicine.disease
ADP-ribosyl Cyclase 1
Leukemia
Lymphocytic
Chronic
B-Cell
Survival Analysis
Gene expression profiling
Immunology
Mutation
biology.protein
Zdroj: Leukemia. 19(5)
ISSN: 0887-6924
Popis: Prognostic predictions in B-cell chronic lymphocytic leukemia (B-CLL) at early clinical stage are based on biological disease parameters, such as ZAP-70 and CD38 protein levels, genomic aberrations as well as immunoglobulin variable heavy chain gene (IgV(H)) mutation status. In the current study, ZAP-70 and CD38 expressions were examined by flow cytometry in 252 patients with B-CLL. Cytoplasmic ZAP-70 expression in more than 20% (ZAP-70(+)) and surface CD38 expression on more than 30% (CD38(+)) of B-CLL cells were associated with an unfavorable clinical course. The levels of ZAP-70 and CD38 did not change over time in the majority of patients where sequential samples were available for analysis. Combined analysis of ZAP-70 and CD38 yielded discordant results in 73 patients (29.0%), whereas 120 patients (47.6%) were concordantly negative and 59 patients (23.4%) were concordantly positive for ZAP-70 and CD38 expression. Median treatment-free survival times in patients whose leukemic cells were ZAP-70(+)CD38(+) was 30 months as compared to 130 months in patients with a ZAP-70(-)CD38(-) status. In patients with discordant ZAP-70/CD38 results, the median treatment-free survival time was 43 months. Thus, ZAP-70 and CD38 expression analyses provided complementary prognostic information identifying three patient subgroups with good, intermediate and poor prognosis. Over-representation of high-risk genomic aberrations such as 17p deletion or 11q deletion and distribution of the IgV(H) mutation status in B-CLL discordant for ZAP-70/CD38 pointed toward a distinct biologic background of the observed disease subgroups. This finding was also supported by microarray-based gene expression profiling in a subset of 35 patients. The expression of 37 genes differed significantly between the three groups defined by their expression of ZAP-70 and CD38, including genes that are involved in regulation of cell survival and chemotherapy resistance.
Databáze: OpenAIRE
Externí odkaz: