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Contact versus contactless signatures in leukemia

ABSTRACT: Gene expression profile (GEP) was analyzed in bone marrow (BM) samples from patients with leukemia or leukemic phase of lymphoma at different time points following aspiration. Among numerous changes in GEP evolved over time a discrete subset of > 60 genes exhibited prompt and sustained switch in expression consistently. Similar results were discovered recently in BM samples from patients with multiple myeloma (GSE36036). GEP was also examined in peripheral blood as well as in BM samples depleted of red blood cells (=WBC) and in cultured cells from some of the patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE39184 | GEO | 2012/07/10

SECONDARY ACCESSION(S): PRJNA170174

REPOSITORIES: GEO

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Contact versus contactless signatures in leukemia

Project description:Gene expression profile (GEP) was analyzed in bone marrow (BM) samples from patients with leukemia or leukemic phase of lymphoma at different time points following aspiration. Among numerous changes in GEP evolved over time a discrete subset of > 60 genes exhibited prompt and sustained switch in expression consistently. Similar results were discovered recently in BM samples from patients with multiple myeloma (GSE36036). GEP was also examined in peripheral blood as well as in BM samples depleted of red blood cells (=WBC) and in cultured cells from some of the patients. Comparative gene expression profiling of whole bone marrow samples from patients with leukemia fixed either immediately following aspiration or after delayed RNA fixation. Comparison was also made between cultured bone marrow cells fixed immediately following spread from the bottom well versus after maintenance in suspension (for 120 minutes).

2012-07-09 | E-GEOD-39184 | biostudies-arrayexpress

Contact versus contactless signatures in myeloma

Project description:The intracellular pathways regulated by intercellular interactions within the myelomatous bone marrow (BM) were studied by analysis of the changes in gene expression profile (GEP) following interruption of the natural interactions due to BM aspiration. Among numerous changes in GEP evolved, a subset of genes exhibited prompt and sustained switch in expression reproducibly. The switch in GEP was reversible and turned “off” and on” in culture conditions resuming cell-cell-matrix contact versus re-spread onto suspension, respectively. Although similar changes in GEP were recorded during remission, various changes were restricted to either the normal or tumor cells. Interestingly, the contact signature was accompanied in culture conditions by stasis as opposed to invasive/expansive potential recognized within the contactless genetic program. This dataset, being unique in disclosing the authentic GEP of MM cells, uncovered contact regulated genes capable of controlling homing, expansion and cell fate. Comparative gene expression profiling of whole bone marrow samples from myeloma patients fixed either immediately following aspiration or after delayed RNA fixation (for 17, 120, 300, 420, 540, 660 minutes). Comparison was also made between cultured bone marrow cells fixed immediately following spread from the bottom well or after maintenance in suspension (for 60, 120 minutes) as well as between malignant pleural fluid sediment fixed before or after cell spread from the bottom tube and maintenance in suspension (for 270 minute).

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Niche modulated versus niche modulating genes in multiple myeloma

Project description:Background. Multiple myeloma (MM) cells depend on the bone marrow (BM) niche for growth and survival. However, the tumor genes regulated by the niche are largely unknown. Design and Methods. BM aspiration samples were obtained from MM-patients with a high tumor load. Gene expression profile (GEP) was recorded immediately following aspiration and at subsequent time points. Identification of niche-regulated genes relied on spontaneous gene modulation following loss of niche regulation. Results. Compared to the reference samples fixed immediately following aspiration, the BM samples fixed after longer delay acquired numerous changes in GEP. The top modulated genes included a common subset of ~ 60 genes displaying prompt and sustained “switch” in expression consistently, among which were oncogenes (FOS, JUN) and genes regulating homing (CD69, RGS1), expansion and angiogenesis (AREG, PTGS2, RGS2, NR4A2). Interestingly, the “switch” in GEP was reversible and turned “off” and “on” in culture conditions resuming cell-cell-matrix contact versus re-spread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of the tumor cells out-of-niche and the regression of the “contactless switch” was followed by induction of a new set of genes this time mostly encoding extracellular proteins, including angiogenic factors (IL8, CXCL5), extracellular-matrix proteins (SPP1, FN1), chemokines (CXCL5, CCL2, CCL20) and growth factors (CCL2, IL6). Conclusions. Our dataset, being unique in authentic expression design, uncovered contact-regulated genes capable of controlling homing, expansion and tumorigenesis. The adaptive response of the tumor cells to culture conditions deficient of integral niche components (e.g., vascular vessels) uncovered inducible niche-regulating tumor genes.

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