Aberrant extrafollicular B cells, immune dysfunction and myeloid inflammation precede malignancy in Waldenstrom macroglobulinemia
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PROVIDER: PRJNA742751 | ENA |
REPOSITORIES: ENA
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Project description:Waldenstrom macroglobulinemia (WM) and its precursor IgM gammopathy are distinct disorders characterized by the growth of mature IgM-expressing B cell clone predominantly in the bone marrow. Here we show that these disorders originate in the setting of expansion of genomically aberrant extrafollicular B cells, immune dysfunction and myeloid inflammation that begins before the expansion of the malignant clone. Host response to these early lesions involves the induction of tumor-specific T cell immunity that may include MYD88 mutation-specific responses. Hematopoietic progenitors carry the oncogenic MYD88 mutations characteristic of the malignant WM clone. These data provide an example of how oncogenic mutations in earlier progenitors may create the milieu promoting the evolution of malignant phenotype in differentiated cells.
2021-11-18 | GSE179221 | GEO
Project description: Not available
| S-EPMC8580616 | biostudies-literature
Project description:In this study, we evaluated clonal Waldenström macroglobulinemia cells with mapping of maturation stages of B cell lymphomagenesis concurrently with the innate and adaptive immune tumor microenvironment in active WM patients (newly diagnosed (NDWM, n = 19) and relapsed or relapsed/refractory (RRWM, n = 42) compared to 10 healthy donors (HD) by mass cytometry.
2022-12-13 | PXD038388 | Pride
Project description:Bone lesion in waldenstom macroglobulinemia (WM) is less common. In the present study, we compaired gene expresion signature of bone lesion in WM compaired to multiple myeloma (MM). In WM, APRIL and HBGB1 were up-regulated compaired to MM.
2020-07-06 | GSE70515 | GEO
Project description:Waldenstom macroglobulinemia (WM) with 6q del is still unknown. In the present study, we analyzed gene expression signiture of WM with 6q del. B-cell receptor signaling pathway, and IL21/IL21-R pathway were up-regulated in WM with 6q del.
2018-10-02 | GSE70511 | GEO
Project description:Exome analyses for the identification of somatic mutation in Waldenstrom macroglobulinemia by comparison of tumor and CD3+(germ line control) population in 16 patients.
transcription profiling of a series of Waldenstrom macroglobulinemia samples
| EGAS00001003603 | EGA
Project description:Total RNA has been isolated from Waldesntrom Macroglobulinemia cell line (BCWM.1; control probe-transfected BCWM1) using RNeasy kit (Qiagen), as described by the manufacturer, and analyzed with the use of Affymetrix U133 plus 2.0 geneChips (Affymetrix). RNA integrity was verified with the Agilent 2100 Bioanalyzer (Agilent, CA,USA).
2008-07-31 | E-MEXP-1739 | biostudies-arrayexpress
Project description:Waldenström’s macroglobulinemia (WM) is a distinct clinicobiological entity defined as a B-cell neoplasm characterized by a lymphoplasmacytic infiltrate in the bone marrow and immunoglobulin M paraprotein production. Cytogenetic analysis is limited by the difficulty in obtaining tumor metaphases and the genetic basis of the disease remains poorly defined. We performed a comprehensive analysis in 42 WM patients by using high-resolution array-based comparative genomic hybridization with the Human Genome 244A microarray. Overall, 83% of samples have chromosomal abnormalities, with a median of three abnormalities per patient (range 0 to 27). The most common abnormality was 6q deletion (40%) and four non-overlapped minimal deleted regions (MDR) were identified. Gain of 6p was the second most common abnormality (17%) and its presence was always concomitant with 6q loss. An interstitial MDR was delineated at 13q14 including MIRN15A and MIRN16-1 in 10% of patients. Other recurrent deletions were 7q22, 8p, 11q22-q23, 11q23-q24 and 17p11-p13 (7% each). Copy gains were identified in chromosomes 18 (17%), 4 (12%), 3 (10%), 8q (10%) and Xq27.1-q28 (10%). To note, we reported biallelic deletions and/or inactivating mutations with uniparental disomy in TRAF3 and TNFAIP3, two negative regulators of the NF-kB signaling pathway. Furthermore, we confirmed the association between TRAF3 inactivation and increased transcriptional activity of NF-kB target genes. Mutational activation of the NF-kB pathway, which is normally activated by ligand-receptor interactions within the bone marrow microenvironment, highlight its biologic importance, and suggest a therapeutic role for inhibitors of NF-KB pathway activation in the treatment of Waldenström’s macroglobulinemia. Keywords: gene expression profiling; array comparative genomic hybridization
2009-08-24 | GSE12668 | GEO
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.
2007-03-01 | E-GEOD-6691 | biostudies-arrayexpress
Project description:Although information on the molecular pathogenesis of Waldenström’s Macroglobulinemia (WM) has greatly improved in recent years, the exact cellular origin and the mechanisms behind WM transformation from IgM MGUS remain undetermined. Here, we undertook an integrative phenotypic, molecular and genomic approach to study clonal B-cells from newly-diagnosed patients with IgM MGUS (n=22), smoldering (n=17), and symptomatic WM (n=10). Through principal-component-analysis of multidimensional flow cytometry data, we demonstrated overlapping phenotypic profiles between clonal B-cells from IgM MGUS, smoldering and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between FACS-sorted clonal B-cells from the three disease stages. Interestingly, while the transcriptome of the Waldenström’s clone was highly deregulated as compared to CD25-CD22+ normal B-cells, significantly less genes were differentially expressed and specific WM pathways down-regulated while comparing the transcriptome of the Waldenström’s clone vs. its normal phenotypic counterpart: CD25+CD22+dim B-cells. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs. symptomatic WM (18% vs. 20% and 73%, respectively; P =.008), suggesting a multistep transformation of clonal B-cells that albeit benign (i.e.: IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström’s clone. Normal bone marrow CD25+ B-cells, Clonal B-Cells from IgM Monoclonal Gammopathy of Undetermined Significance, and Clonal B-Cells from Waldenström's Macroglobulinemia
2015-05-05 | E-GEOD-61597 | biostudies-arrayexpress