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E-GEOD-61597 - The cellular origin and malignant transformation of Waldenström's Macroglobulinemia [gene expression]

Status
Released on 5 May 2015, last updated on 9 May 2015
Organism
Homo sapiens
Samples (31)
Array (1)
Protocols (6)
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
Experiment type
transcription profiling by array 
Contacts
Bruno Paiva <bpaiva@unav.es>, Abelardo Bárez, Alberto Orfao, Alfonso G de Coca, Cristina Jimenez, Emilia Pardal, Enrique M Ocio, Fernando Escalante, Jesús F San Miguel, Jose J Perez, Josefina Galende, José Alonso, José Hernández, Luis A Corchete, Magdalena Sierra, Maria E Sarasquete, Maria L Sánchez, Maria-Belen Vidriales, Maria-Carmen Montes, Maria-Victoria Mateos, Noemi Puig, Norma C Gutierrez, Paloma Barcena, Ramón García-Sanz, Rebeca Cuello, Tomás J González-López
Citation
The cellular origin and malignant transformation of Waldenstr�m macroglobulinemia. Paiva B, Corchete LA, Vidriales MB, Garc�a-Sanz R, Perez JJ, Aires-Mejia I, Sanchez ML, Barcena P, Alignani D, Jimenez C, Sarasquete ME, Mateos MV, Ocio EM, Puig N, Escalante F, Hern�ndez J, Cuello R, Garc�a de Coca A, Sierra M, Montes MC, Gonz�lez-L�pez TJ, Galende J, B�rez A, Alonso J, Pardal E, Orfao A, Gutierrez NC, San Miguel JF.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-61597.idf.txt
Sample and data relationshipE-GEOD-61597.sdrf.txt
Raw data (1)E-GEOD-61597.raw.1.zip
Processed data (1)E-GEOD-61597.processed.1.zip
Array designA-AFFY-141.adf.txt
Links