Single Cell Analysis of MYD88 L265P and MYD88 WT Waldenström Macroglobulinemia Patients

Waldenström macroglobulinemia (WM) is a low-grade B- cell lymphoproliferative disorder characterized by bone marrow (BM) infiltration by small lymphoplasmacytic lymphoma (LPL) cells that secrete monoclonal IgM immunoglobulin. Our understanding of the pathogenesis of WM has improved significantly by the discovery that the vast majority of patients with WM harbor the somatic mutation L265P in MYD88 gene on their clonal cells. However, the small fraction of patients (3-10%) that lack mutations in MYD88 is characterized by a different clinical course, with an increased risk of disease transformation and probably shorter overall survival. WM is a clonal disease but there may be significant heterogeneity within the clone, which may be associated with clinical outcomes, however, this has not been extensively explored. Recent advances in the area of single-cell RNA sequencing (scRNA-Seq) technologies have improved so that it is feasible to sequence and analyze thousands of cells per tumor delivering significant insights into a tumor's cellular heterogeneity and the biological features that distinguish different cell populations.