Research Strategy

In recent years we have witnessed substantial progress in basic biomedical research and subsequent clinical management of WM. IWMF funded research has been so successful in making these advances in part because of its rigorous requirements for awarding grants, which includes a review by an independent committee composed of selected members of the IWMF Scientific Advisory Committee and other experts in the field. The IWMF Board of Trustees also must approve the research grants to be funded, and oversight by IWMF continues after the grants are awarded. Researchers who receive grant awards are required to submit periodic progress reports to the IWMF Research Committee for review and comment.

WM funded research should be guided by the pillars listed below.

Pillars of WM Research

• WM Cell Biology: Includes research into signaling pathways driving the growth and survival of WM. Also includes are preclinical testing of novel therapeutic strategies and research into signaling mechanisms related to recurrent somatic mutations such as MYD88, CXCR4 and ARID1A as well as WM specific dysregulation of novel and established pathways such NF-kB, ERK, and PI3K/AKT.

• T-Cell Based Therapeutics: Includes development and preclinical testing of CAR-T and bi- and tri-specific antibodies, as well as the development of novel therapeutic strategies that promote immune anti-WM engagement. Also includes proposals to overcome T-cell anergy and counter the immunosuppressive effects associated with myeloid derived suppressor cells and similar mechanisms.

• Microenvironmental Research: Like many indolent lymphomas, WM cannot survive without the support of its local environment. This pillar supports research into identifying these dependencies and assessing their therapeutic potential. It also supports the development of organoids and xenograft models that can support long-term primary WM cultures for research and testing. This includes changes in microenvironmental composition, signaling, and spatial relationships associated with disease progression and response. In addition to T-cell exhaustion and immune dysregulation studies from the previous pillar, it also supports the development of organoids and xenograft models that can support long term primary WM cultures for research and testing.

• Genomic, Epigenomic, and Transcriptional Research: Supports bulk, single cell, and spatial studies to better understand the biology of WM evolution from MGUS to symptomatic disease, as well as mechanisms driving primary and acquired therapeutic resistance. This pillar further supports related research into identification of high-risk features, novel target identification, and biological characterization of WM disease manifestations such as Bing Neel Syndrome and transformation.

• Proteomics: This pillar is distinct from the previous one as it focuses on protein properties and modifications that impact key WM signaling pathways or can be used for prognostic testing in a manner distinct from the underlying genetics. It also supports protein-based research into the causes and treatment of cryoglobulinemia, cold agglutinins, amyloid, demyelinating neuropathy, and other complications associated with the IgM paraprotein.