A new case study looking at the evolution of follicular lymphoma shows for the first time how the blood cancer develops inside the human body. This insight is giving scientists a first look at how a common malignant ancestor can be passed from donor to recipient.
The phenomenon of a donor passing a malignancy to a recipient is well-documented, but considered a minimal risk to those in the transplant community says David Weinstock, M.D., an assistant professor of medicine at Dana-Farber Cancer Institute.
He says what is unique about this case, dubbed "The Study of Two Sisters", is it’s giving scientists an rare opportunity to better understand the genetic abnormalities that led to grade 2/3A follicular lymphoma developing in biological sisters after one donated bone marrow to the other. This insight may translate into earlier treatment for future lymphomas.
The study involves a 41-year-old woman diagnosed with chronic-phase chronic myeloid leukemia, who received a bone marrow transplant and subsequent leukocyte infusion from her sister. These treatments controlled her leukemia, but seven years later, each sister developed follicular lymphoma, a common type of non-Hodgkin Lymphoma (NHL) that begins in certain white blood cells (lymphocytes) and adversely affects the person’s immune system.
“We were able to combine clinical activity with laboratory expertise to gain a real insight into the biology involved,” says Dr. Weinstock, lead author of the case study, published first online in the December 2011 issue of Cancer Discovery, a professional journal of the American Association for Cancer Research. The findings were presented on Dec. 12, at the 2011 American Society of Hematology Annual Meeting and Exposition in San Diego, Calif.
Weinstock and his colleagues sequenced the DNA of samples derived from each of the sisters as well as a frozen sample of the white blood cell (leukocyte) infusion to determine the genetic lesions that led to the lymphoma.
They found that each sister had identical human antibody BCL2/IGH gene mutations which occurs in 90 percent of follicular lymphomas, and the same variable, diverse and joining or V(D)J gene segment rearrangement, found in this type of dysfunctional tumor cells.
The researchers also identified 15 mutations that were present in both lymphomas.
Perhaps most relevant, researchers used technologically-advanced ultrasensitive DNA sequencing equipment to recover 14 of these mutations from the donor lymphocyte infusions, suggesting a lymphoma ancestor harboring these genetic alterations was passed from the donor to the recipient seven years before their diagnoses.
Weinstock said by written statement this knowledge could lead to an early treatment for follicular lymphoma in the future.
NHL is the seventh most common cancer type in the United States and the number of people with NHL continues to climb. According to American Cancer Society estimates, more than 66,000 people — adults and children — will be diagnosed with NHL in 2011. But people with NHL have more treatment options than ever before.
“Currently the only curative approach is stem cell transplantation, but the more we understand about the genetic aberrations that lead to follicular lymphoma, the better we’ll be able to manage the disease,” Weinstock said.
Both sisters are now in remission after standard chemotherapy treatment. The study was funded by a Stand Up To Cancer Innovative Research Grant.
The Genentech website has more NHL patient and treatment information.
The Cleveland Clinic has more information on leukocyte infusion at http://my.clevelandclinic.org/services/donor_leukocyte_infusion/hic_donor_leukocyte_infusion.aspx
Lynette Summerill, an award-winning writer and scuba enthusiast lives in San Diego, CA with her husband and two beach loving dogs. In addition to writing about cancer-related issues for EmpowHER, her work has been seen in newspapers and magazines around the world.
Molecular Ontogeny of Donor-Derived Follicular Lymphomas Occurring after Hematopoietic Cell Transplantation. Oliver Weigert, Nadja Kopp, Andrew A. Lane, Akinori Yoda, Suzanne E. Dahlberg, Donna Neuberg, Anita Y. Bahar, Bjoern Chapuy, Jeffery L. Kutok, Janina A. Longtine, Frank C. Kuo, Terry Haley, Maura Salois, Timothy J. Sullivan, David C. Fisher, Edward A. Fox, Scott J. Rodig, Joseph H. Antin, and David M. Weinstock. Cancer Discovery. December 12, 2011 ; Published OnlineFirst December 12, 2011; doi: 10.1158/2159-8290.CD-11-0208. Abstract at: http://cancerdiscovery.aacrjournals.org/content/early/2011/12/08/2159-8290.CD-11-0208
Immunogistochemistry of IgH and bcl-2 genes confirming diagnosis of follicular lymphoma. Accessed online 12 December 2011 at:
AACR News Release. Study of Two Sisters Sheds Light on Lymphoma Evolution. Jeremy Moore. 9 December 2011.
American Cancer Society. What is NHL? Accessed online 12 December 2011.
Reviewed December 13, 2011
by Michele Blacksberg RN
Edited by Jody Smith
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