Transcriptomics

Dataset Information

3

The cellular origin and malignant transformation of Waldenström's Macroglobulinemia [copy number variation]


ABSTRACT: 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. Copy number analysis using the Affymetrix CytoScan 750K Array to study clonal B-cells from newly-diagnosed patients with IgM MGUS, smoldering, and symptomatic WM. Peripheral T-cells from paired and unpaired controls were also assessed.

ORGANISM(S): Homo sapiens  

SUBMITTER: Maria E Sarasquete   Cristina Jimenez  Alberto Orfao  Maria-Victoria Mateos  Maria-Belen Vidriales  Norma C Gutierrez  Luis A Corchete  Emilia Pardal  Jesús F San Miguel  Jose J Perez  Enrique M Ocio  Tomás J González-López  Alfonso G de Coca  Magdalena Sierra  José Hernández  Maria L Sánchez  Noemi Puig  Abelardo Bárez  Maria-Carmen Montes  Paloma Barcena  Fernando Escalante  José Alonso  Josefina Galende  Rebeca Cuello  Ramón García-Sanz  Bruno Paiva 

PROVIDER: E-GEOD-61650 | ArrayExpress | 2015-05-06

SECONDARY ACCESSION(S): GSE61650PRJNA261789

REPOSITORIES: GEO, ArrayExpress

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Publications


Although information about the molecular pathogenesis of Waldenström macroglobulinemia (WM) has significantly advanced, the precise cell of origin and the mechanisms behind WM transformation from immunoglobulin-M (IgM) monoclonal gammopathy of undetermined significance (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 = 16), and symptomatic WM (n = 1  ...[more]

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