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Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells.

ABSTRACT: 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.

SUBMITTER: Vallat LD

PROVIDER: S-EPMC1874586 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells.

Vallat Laurent D LD Park Yuhyun Y Li Cheng C Gribben John G JG

Blood 20070118 9

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 ...[more]

PMID: 17234734

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Project description:Study objectivesTemporal expectation enables us to focus limited processing resources, thereby optimizing perceptual and motor processing for critical upcoming events. We investigated the effects of total sleep deprivation (TSD) on temporal expectation by evaluating the foreperiod and sequential effects during a psychomotor vigilance task (PVT). We also examined how these two measures were modulated by vulnerability to TSD.DesignThree 10-min visual PVT sessions using uniformly distributed foreperiods were conducted in the wake-maintenance zone the evening before sleep deprivation (ESD) and three more in the morning following approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were determined by a tertile split of participants based on the change in the number of behavioral lapses recorded during ESD and TSD. A subset of participants performed six additional 10-min modified auditory PVTs with exponentially distributed foreperiods during rested wakefulness (RW) and TSD to test the effect of temporal distribution on foreperiod and sequential effects.SettingSleep laboratory.ParticipantsThere were 172 young healthy participants (90 males) with regular sleep patterns. Nineteen of these participants performed the modified auditory PVT.Measurements and resultsDespite behavioral lapses and slower response times, sleep deprived participants could still perceive the conditional probability of temporal events and modify their level of preparation accordingly. Both foreperiod and sequential effects were magnified following sleep deprivation in vulnerable individuals. Only the foreperiod effect increased in nonvulnerable individuals.ConclusionsThe preservation of foreperiod and sequential effects suggests that implicit time perception and temporal preparedness are intact during total sleep deprivation. Individuals appear to reallocate their depleted preparatory resources to more probable event timings in ongoing trials, whereas vulnerable participants also rely more on automatic processes.

Dataset Information

Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells.

Publications

Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells.

Similar Datasets

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