Molecular pathogenesis of Waldenstrom's macroglobulinemia

Abstract

Waldenström's macroglobulinemia is an indolent, lymphoproliferative disease, characterized by a heterogeneous lymphoplasmacytic bone marrow infiltrate and high immunoglobulin M production. While technological advances over the past several decades have dramatically improved the possibilities of studying the molecular basis of Waldenström's macroglobulinemia, the pathogenesis of the disease remains fragmented. Undoubtedly, research has been successful in uncovering underlying aberrations and deregulated mechanisms in this disease, providing useful information for identifying biomarkers for disease diagnosis, risk stratification and therapeutic intervention, but there is still a long way to go before the pathogenesis of Waldenström's macroglobulinemia is fully revealed. In addition, the low number of in vitro or in vivo models significantly challenges extensive analysis. In this manuscript, we review the molecular basis of this disease.

Figure 1.

Overview of the copy-number abnormalities identified in WM by aCGH. Chromosomes 1 to Y are represented from left to right. Red blocks represent chromosome gains, whereas blue blocks represent chromosome losses. The amplitude in each abnormal region represents the frequency of each copy-number abnormality. Adapted from Braggio et al.

Figure 2.

Schematic representation of MyD-88 dependent TLR signaling pathway.

Figure 3.

Schematic representation of the PI3K/Akt/mTOR pathway. The pathway provides several targets for specific therapies. Drugs targeting the pathway are shown in red boxes.