Torch January 2021 Issue 22.1 International Waldenstrom’s Macroglobulinemia Foundation INSIDE THIS A GLANCE AT THE TUMOR MICROENVIRONMENT ISSUE IN WALDENSTROM MACROGLOBULINEMIA A Glance at the Tumor By Shahrzad Jalali, PhD Microenvironment in Waldenstrom Macroglobulinemia .... 1 Editor’s note: Dr. Shahrzad Jalali has been a research associate in the Division of Hematology at Mayo Today, Tomorrow, Clinic Rochester since 2015. She received her PhD in and Beyond................ 6 biochemistry and medical genetics from the University of Manitoba, Canada, and obtained her postdoctoral IWMF Leadership trainings from Princess Margaret Cancer Centre and Passes the Torch ....... 8 Hospital for Sick Children, University of Toronto, where she studied malignant brain tumors. She currently Torch Toon .................... 9 works as a research associate within the lymphoma group at Mayo Clinic, and her research is focused on IWMF Funded Research: B-cell lymphomas, with a primary focus on Waldenstrom Progress Report ....... 10 macroglobulinemia (WM). Dr. Jalali is investigating the contribution of the bone marrow microenvironment in IWMF Funded Research: New 2020 Grants ...... 11 WM pathogenesis. She was the recipient of an IWMF-LLS Strategic Research Roadmap grant in 2017, as well as an Dr. Shahrzad Jalali IWMF Young Investigator Award in 2016 and 2018. The An Important New Career Development results of her work in WM have appeared as peer-reviewed articles in the past five years, Program for Young and her contribution to the field is ongoing. Investigators ............. 13 The human immune system is composed of a wide variety of cell types, including B-cells, Navigating My Life with T-cells, mast cells, neutrophils, macrophages, and monocytes. While the functions of all these Waldenstrom’s ..........14 cell types are necessary to maintain the equilibrium of the immune system, B-cells are central to humoral immunity, which is the part of the immune system that combats invading pathogens Medical News by producing and secreting antigen-specific immunoglobulins (Ig), also called antibodies. Roundup ................... 15 B-cells originate from immature cells called multipotent hematopoietic stem cells and common How You Can Get lymphoid progenitor cells in the bone marrow and undergo the steps of maturation to express Involved in WM immunoglobulins of different classes (IgM and IgD) on their cell surface; then they leave the Research .................. 20 bone marrow to enter secondary or peripheral lymphoid tissues, such as the lymph nodes and Australian Michael Van spleen. In the peripheral tissues, B-cells complete their development and eventually become Ewijk Rides 702 Km specialized plasma cells that secrete large amounts of the same type of antibodies found on their for a Fundraiser ........ 24 cell surfaces (Figure 1). During this process, B-cells that recognize self-antigens are removed, a process called negative selection, in order to protect one’s own body tissues from the effects Remembering Cindy Lou Furst ........ 25 of B-cell-specific autoimmune responses. Understanding the detailed molecular events that control the differentiation of normal B-cells Support has been instrumental in helping to identify the origin of Waldenstrom macroglobulinemia Group News ............. 26 (WM), which is a low-grade B-cell lymphoma. The pathogenesis of WM is due to the International Scene .... 28 infiltration and growth of malignant B-cells, primarily referred as lymphoplasmacytic lymphoma cells, within the bone marrow where they live, proliferate, and secrete large From IWMF Connect: amounts of immunoglobulin class M (IgM), thereby disrupting the equilibrium of the bone Winter 2021 .............. 32 marrow. A Glance, cont. on page 3 FOUNDER OFFICE & PROJECT MANAGER, INFORMATION Arnold Smokler MANAGER & SUPPORT PRESIDENT EMERITA Donna Cutillo Michelle Postek Judith May DIRECTOR, DEVELOPMENT & MANAGER, MEETINGS & PRESIDENT EMERITUS COMMUNICATIONS PARTNER ENGAGEMENT Carl Harrington Jeremy Dictor Sara McKinnie PRESIDENT & CEO Newton Guerin CHAIR OF THE BOARD IWMF SCIENTIFIC ADVISORY COMMITTEE Peter DeNardis Stephen Ansell, MD, Co-Chair Efstathios Kastritis, MD Mayo Clinic University of Athens, School of Medicine SECRETARY-TREASURER Steven Treon, MD, Co-Chair Beverly Docteur Dana-Farber Cancer Institute Eva Kimby, MD Karolinska Institute, Sweden VICE CHAIRS James R. Berenson, MD Institute for Myeloma & Véronique Leblond, MD Tom Hoffmann, MD Hôpital Pitié Salpêtrière, France Michael Sesnowitz Bone Cancer Research Lisa Wise Christian Buske, MD Monique Minnema, MD University Ulm, Germany UMC Utrecht, Netherlands BOARD OF TRUSTEES Jorge Castillo, MD Gwen Nichols, MD Stephen Ansell, MD Dana-Farber Cancer Institute Leukemia & Lymphoma Society Ron Branscome Glenn Cantor Morton Coleman, MD Roger Owen, MD Shirley Ganse Weill Cornell Medical College St. James’s Institute of Oncology, United Kingdom Paul Kitchen Meletios A. Dimopoulos, MD Carl Lisman School of Medicine Lia Palomba, MD Meg Mangin University of Athens, Greece Memorial Sloan Kettering Linda Nelson Cancer Center Stanley Frankel, MD BOARD ADVISOR Columbia University Surinder Sahota, PhD Steven Treon, MD University of Southampton, Morie Gertz, MD United Kingdom Mayo Clinic FINANCE MANAGER Sheeba Thomas, MD Robin Tucker Irene Ghobrial, MD MD Anderson Cancer Center Dana-Farber Cancer Institute Brian Van Ness, PhD DIGITAL & CREATIVE Zachary Hunter, PhD University of Minnesota SERVICES MANAGER Dana-Farber Cancer Institute Maureen Baeck The IWMF Torch is a publication of IWMF. This publication is designed to provide information about the disease Waldenstrom’s macroglobulinemia. It is distributed as a member service by the International Waldenstrom’s Macroglobulinemia Foundation, Inc., to those who seek information on Waldenstrom’s macroglobulinemia with the understanding that the Foundation is not engaged in rendering medical advice or other professional medical services. EDITOR IWMF CONNECT FORMATTING & Shirley Ganse Jacob Weintraub, MD PRODUCTION ASSOCIATE EDITOR INTERNATIONAL Sara McKinnie Sue Herms CORRESPONDENT TORCH ADVISOR 6144 Clark Center Avenue SUPPORT GROUP NEWS Annette Aburdene Peter DeNardis Sarasota, FL 34238 Chris Stay CARTOONIST Telephone 941-927-4963 SCIENCE EDITOR Linda Pochmerski Fax 941-927-4467 Glenn Cantor E-mail: [email protected] IWMF is a 501(c)(3) tax exempt non-profit organization Fed ID #54-1784426. Waldenstrom's macroglobulinemia Website: www.iwmf.com is coded 273.3 in the International Classification of Diseases (ICD) of the World Health Organization. A Glance, cont. from page 1 Recent studies have shown that the malignant B-cells of microenvironment. They have shown that there is a protein WM are unable to go through the process called class factor, called chemokine stromal derived factor-1 (SDF-1), switch recombination, during which proliferating B-cells which is highly expressed in the bone marrow of WM switch the expression of one class of immunoglobulins to patients. The receptor for this factor, called CXCR4, is another when encountering foreign antigens. An example found on the surface of WM cells. The interaction between would be switching from IgM class to IgG or IgA class. SDF-1 and CXCR4 mediates migration of the WM cells out of the blood vessels. Indeed, approximately 30% of The bone marrow niche WM patients have elevated levels of CXCR4 molecules As a main location for the infiltration and proliferation of on the surface of their WM cells, due to its altered genetic malignant B-cells, the bone marrow microenvironment structure. This increased CXCR4 expression, together with plays a key role in the pathogenesis of WM. The architecture an increase in SDF-1 level, could increase the CXCR4/ of the bone marrow is composed of both cellular and non- SDF-1 interaction and the homing of WM cells in the bone cellular compartments. The cellular compartments of the marrow. Increased survival of WM cells also impacts their bone marrow contain blood cells and their precursors migration and homing in the bone marrow. (such as B-cells, T-cells, neutrophils, monocytes, and red blood cells), as well as non-blood cells (including cells The role of non-cellular/soluble factors of the bone that produce fat, bone, and blood vessel tissues). The marrow in WM non-cellular components of the bone marrow involve Cytokines and chemokines are among the non-cellular extracellular matrix, cytokines, chemokines, growth soluble factors of the bone marrow and act as messenger factors, and metabolites. Indeed, there is a complex, yet molecules that bind to their receptors on cell surfaces and harmonized, array of interactions between cellular and regulate signaling cascades within the cells. Cytokines non-cellular components of the bone marrow that not only regulate differentiation of B-cells into plasma cells and controls continued existence of the hematopoietic stem facilitate plasma cell equilibrium and immunoglobulin and progenitor cells, but also determines their ability to secretion in the bone marrow. For instance, interleukin-21 generate different blood cells under normal and healthy (IL-21) is a cytokine known to regulate normal B-cell conditions. Here we highlight some of the findings related function and B-cell differentiation into immunoglobulin- to the mechanism by which WM cells home to the bone producing plasma cells. B-cell activating factor (BAFF), marrow as well as the contribution of both cellular and non- also called B-lymphocyte stimulator (BLyS), is another cellular factors