Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells.
Gene expression in cells is a dynamic process but is usually examined at a single time point. We used gene expression profiling over time to build temporal models of gene transcription after B-cell receptor (BCR) signaling in healthy and malignant B cells and chose this as a model since BCR cross-linking induces both cell proliferation and apoptosis, with increased apoptosis in chronic lymphocytic leukemia (CLL) compared to healthy B cells. To determine the basis for this, we examined the global temporal gene expression profile for BCR stimulation and developed a linear combination method to summarize the effect of BCR simulation over all the time points for all patients. Functional learning identified common early events in healthy B cells and CLL cells. Although healthy and malignant B cells share a common genetic pattern early after BCR signaling, a specific genetic program is engaged by the malignant cells at later time points after BCR stimulation. These findings identify the molecular basis for the different functional consequences of BCR cross-linking in healthy and malignant B cells. Analysis of gene expression profiling over time may be used to identify genes that might be rational targets to perturb these pathways.
Vallat
Laurent D
LD
Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Park
Yuhyun
Y
Li
Cheng
C
Gribben
John G
JG
D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors
D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell