Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The cellular origin and malignant transformation of Waldenström's Macroglobulinemia [gene expression]

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. Normal bone marrow CD25+ B-cells, Clonal B-Cells from IgM Monoclonal Gammopathy of Undetermined Significance, and Clonal B-Cells from Waldenström's Macroglobulinemia

ORGANISM(S): Homo sapiens

SUBMITTER: Bruno Paiva

PROVIDER: E-GEOD-61597 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The cellular origin and malignant transformation of Waldenström macroglobulinemia.

Paiva Bruno B Corchete Luis A LA Vidriales Maria-Belen MB García-Sanz Ramón R Perez Jose J JJ Aires-Mejia Irene I Sanchez Maria-Luz ML Barcena Paloma P Alignani Diego D Jimenez Cristina C Sarasquete Maria-Eugenia ME Mateos María-Victoria MV Ocio Enrique M EM Puig Noemi N Escalante Fernando F Hernández José J Cuello Rebeca R García de Coca Alfonso A Sierra Magdalena M Montes Maria-Carmen MC González-López Tomás J TJ Galende Josefina J Bárez Abelardo A Alonso José J Pardal Emilia E Orfao Alberto A Gutierrez Norma C NC San Miguel Jesús F JF

Blood 20150205 15

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]

PMID: 25655603

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Dataset Information

The cellular origin and malignant transformation of Waldenström's Macroglobulinemia [gene expression]

Publications

The cellular origin and malignant transformation of Waldenström macroglobulinemia.

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