Hyaluronan Synthases and RHAMM as Synergistic Mediators of Malignancy in B Lineage Cancers

Hyaluronan synthases (HASs), enzymes that synthesize hyaluronan (HA), are overexpressed, and in the case of HAS1, undergo aberrant splicing in some B lineage malignancies, including multiple myeloma (MM) and Waldenstrom’s macroglobulinemia (WM). RHAMM, the receptor for HA-mediated motility, is overexpressed in malignant B lineage cells from WM, in nonHodgkin’s lymphoma (NHL), B cell chronic lymphocytic leukemia (B-CLL) and in MM. HAS1 and the HAS1 splice variants correlate with poor survival in MM. Elevated expression of the RHAMM splice variant also correlates strongly with reduced patient survival in MM, confirming the clinical impact of HASs and of RHAMM variant expression. We speculate that synergistic interactions between HASs, HA and RHAMM may underlie increasingly aggressive disease and the generation of chromosomal instability in MM.