August 30, 2012: New England Journal of Medicine (DOI:10.1056/NEJMoa1200710): A team of scientists at the Bing Center for Waldenstrom’s Macroglobulinemia at the Dana Farber Cancer Institute and Harvard Medical School in Boston, MA led by Steven P. Treon MD, PhD announced the identification of a gene mutation that underlies most cases of Waldenstrom’s Macroglobulinemia. The research which was first presented at the 53rd Annual Meeting of the American Society of Hematology and then at the 7th International Workshop on WM described a mutation occurring in one single DNA molecule out of three billion DNA molecules which make up the genetic code of a cell, as the leading culprit in Waldenstrom’s and a target for new diagnostic tests and drug development for this disease. The mutation was discovered after the team performed whole genome sequencing of tumor and normal cells from thirty patients with Waldenstrom’s Macroglobulinemia. By lining up and comparing the DNA sequences of tumor and normal cells, Treon and his colleagues were able to detect the same recurring mutation in the MYD88 gene, a finding present in ninety percent of patients with Waldenstrom’s Macroglobulinemia who were tested. In most patients the L265P mutation was found in one of the 2 copies of the MYD88 gene, but in some patients with a longstanding history of WM, a reduplication of the segment of chromosome 3 where MYD88 is located resulted in 2 copies of the L265P mutation being present. The clinical significance of having an extra copy of the mutation remains to be determined.
Feb 13, 2013: Ibrutinib receives breakthrough designation for mantle cell lymphoma and Waldenstrom's Macroglobulinemia: Researchers at the Bing Center identified a mutation in MYD88 gene which was reported last year in the New England Journal of Medicine that affects over 90% of patients with WM, and activates Bruton’s Tyrosine Kinase (BTK) that permits the growth and survival of WM cells.
April 21, 2013: Dr. Steven Treon delivered a lecture to the New England Support Group on Genomic and Clinical Advances in Waldenstrom's Macroglobulinemia. This lecture was given at the Jimmy Fund Auditorium, Dana-Farber Cancer Institute, Boston, MA. Click here to view the lecture in its entirety.
The WM Macroglobulinemia Clinic at the DFCI is devoted to the care of patients with Waldenstrom's Macroglobulinemia and related IgM disorders, including IgM MGUS, Myeloma and Neuropathies.
Plasma cell regulatory pathways in WM. In recent studies, we have attempted to dissect the molecular mechanisms which prevent WM cells from fully differentiating into plasma cells. Ordinarily, B-cells mature in a defined manner passing through the mature B-cell stage to lymphoplasmacytic cells, and then onto mature plasma cells. Mature plasma cells make antibodies that serve to protect us against pathogens, and typically include the IgA and IgG antibodies.