Dataset Information

Transcriptome analysis of in vitro generated plasmablasts dervied from Waldenström macroglobulinemia (WM) or heathly control B-cells

ABSTRACT: The ability to model WM B-cell differentiation using an in vitro system was validated in comparison to healthy cells. The stimuli used initially were CD40L and F(ab’)2 anti-IgG/M, a combination which mimics T-cell dependent activation. Using these conditions, WM B-cells generated mature plasma cells that closely resemble those from healthy controls. Since WM cells harbour the characteristic gain-of-function MYD88L265P mutation, it was also of interest to determine the impact of TLR signals on the differentiation process. In contrast to the expectation of enhanced survival, WM cells exhibited a profoundly deleterious response to R848 + F(ab’)2 anti-IgG/M stimulation, with a sharp decline in population from the initiation of culture and a failure to generate plasma cells. RNA sequencing was performed on material harvested from differentiating cells at day 6 of culture within the in vitro system to assess the underlying gene expression changes that accompanied the two types of stimulation. The samples consisted of 3 healthy controls with matched samples for both CD40L and R848 stimulation and a total of 6 WM samples. Examination of the transcriptomes revealed that WM plasmablasts exhibit elevated expression levels of genes associated with TLR and NF-κB signaling, but reduced levels of genes associated with plasma cell re-programming. This is particularly pronounced in cells treated with the TLR7 agonist R848, suggesting an uncoupling of TLR signaling from plasma cell differentiation in WM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139671 | GEO | 2020/05/13

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:The tumoral clone of Waldenstrons macroglobulinemia (WM) shows a wide morphological heterogeneity which ranges from B-lymphocytes (BL) to plasma cells (PC). By means of genome-wide expression profiling we have been able to identify genes exclusively deregulated in BL and PC from WM, but with a similar expression pattern in their corresponding cell-counterparts from CLL and MM, as well as normal individuals. The differentially expressed genes have important functions in B-cell differentiation and oncogenesis. Thus, two of the genes down-regulated in WM-BL were IL4R, which plays a relevant role in CLL B cell survival, and BACH2 that participates in the development of class-switched PC. Interestingly, one of the up-regulated genes in WM-BL was IL6. A set of 4 genes was able to discriminate clonal B-lymphocytes from WM and CLL: LEF1 (WNT/ßcatenin pathway), MARCKS, ATXN1 and FMOD. We also found deregulation of genes involved in plasma cell differentiation such as PAX5 which was overexpressed in WM-PC, and IRF4 and BLIMP1 which were underexpressed. In addition, three of the target genes activated by PAX5 -CD79, BLNK and SYK- were up-regulated in WM-PC. In summary, these results indicate that both PC and BL from WM are genetically different from the MM and CLL cell-counterpart. Keywords: Waldenstrons macroglobulinemia, expression profiling, microarrays, Affymetrix. Bone marrow (BM) samples from 10 patients with Waldenstrons macroglobulinemia (WM), 12 with multiple myeloma (MM) and 11 with chronic lymphocytic leukemia (CLL) were included in the study. All samples corresponded to newly diagnosed untreated patients. In addition, 8 normal B lymphocytes samples (NBL) from peripheral blood and 5 normal plasma cells (NPC) from bone marrow of healthy donors were also selected in order to relate the deregulation of GEP of clonal populations to normal condition. The study was approved by the local research ethics committee and written informed consent was obtained from all patients and healthy donors.

Dataset Information

Transcriptome analysis of in vitro generated plasmablasts dervied from Waldenström macroglobulinemia (WM) or heathly control B-cells

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure