Gene Expression Profiling of Waldenstrm's Macroglobulinemia vs. IgM Monoclonal Gammopathy of Undetermined Significance


J Blood Disord. 2014;1(2): 2.

Gene Expression Profiling of Waldenström's Macroglobulinemia vs. IgM Monoclonal Gammopathy of Undetermined Significance

Alessandra Trojani1*, Antonino Greco1, Alessandra Tedeschi1, Milena Lodola1, Barbara Di Camillo2, Anna Maria Frustaci1, Roberto Cairoli1, Enrica Morra1

1Department of Hematology, Niguarda Hospital, Milan,Italy

2Department of Information Engineering, University of Padova, Italy

*Corresponding author: Alessandra Trojani, Department of Hematology, Niguarda Hospital, Piazza Ospedale Maggiore 3, 20162, Milano, Italy.

Received: September 30, 2014; Accepted: October 01,2014; Published: October 07, 2014


Waldenstrom's Macroglobulinemia; IgM Monoclonal gammopathy of undetermined significance; Gene profiling


Waldenstrom's Macroglobulinemia (WM) is an incurable B-lymphoproliferative disorder, characterized by the infiltration of Bone Marrow (BM) by a heterogeneous population of small B lymphocytes with variable plasmacytoid differentiation, as well as mature plasma cells, along with the presence of an IgM monoclonal gammopathy in the blood [1,2].

IgM Monoclonal gammopathy of undetermined significance (IgM-MGUS) is an asymptomatic condition determined only by the presence of a monoclonal immunoglobulin (M protein) [3,4]. Significantly, patients with IgM-MGUS show an increased risk of developing WM [5]. The rate of progression from IgM-MGUS to WM has been noted to be 1.5-2% a year [6].

WM (symptomatic and indolent) and IgM-MGUS can be identified based on two main features, the bone marrow infiltration and the existence of symptoms while the different biological and genetic characteristics need to be explored.

In this study we performed microarray analysis of WM and IgMMGUS patients in order to define the molecular signature of WM B cells as well as plasma cells compared to their counterparts from IgM-MGUS. Our aim was to identify genes differently expressed and pathways distinguishing WM from IgM-MGUS in order to determine the molecular and biological mechanisms typical for each disorder.

We isolated BM CD19+ as well as CD138+ cells of 36 WM and 13 IgM-MGUS using Miltenyi Microbeads and we performed expression analysis with Affymetrix GeneChip HG U133 Plus 2.0 Array.

Data was processed using RMA and analyzed using SAM and a false discovery rate threshold of 5% to select the differentially expressed genes. To further select a subset of robust biomarkers, SVMs were used in a Monte Carlo bootstrap resampling schema with B=100 external training/test splits to discriminate between WM and IgM-MGUS.

No different genes were found from the comparison between WM vs. IgM-MGUS CD138+ cells.

641 probes were selected by SAM on CD19+ cells. SVMs permitted the selection of 66 robust biomarker genes with MCC accuracy on external samples equal to 0.87. Functional enrichment analysis demonstrated the involvement of the following pathways:

In conclusion, GEP of BM CD19+ cells demonstrated that 66 genes were robust biomarkers able to distinguish between WM and IgMMGUS. The negative regulation of translation, pro-/anti-apoptotic processes, Notch signaling pathway, Purine/Pyrimidine metabolism, Sphingolipid metabolism and the regulation of transcription were mostly involved in the comparison between WM and IgM-MGUS.


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Citation: Trojani A, Greco A, Tedeschi A, Lodola M, Camillo BD, et al. Gene Expression Profiling of Waldenström's Macroglobulinemia vs. Igm Monoclonal Gammopathy of Undetermined Significance. J Blood Disord. 2014;1(2): 1008. ISSN 2379-8009.

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