Tag Archives: bone marrow

stem.cell

TGen researchers uncover root of myeloma relapse

Researchers have discovered why multiple myeloma, a difficult to cure cancer of the bone marrow, frequently recurs after an initially effective treatment that can keep the disease at bay for up to several years.

Working in collaboration with colleagues at Princess Margaret Hospital in Toronto, researchers from Mayo Clinic in Arizona and the Translational Genomics Research Institute (TGen) in Phoenix were part of the team that conducted the study published in the Sept. 9 issue of Cancer Cell.

The research team initially analyzed 7,500 genes in multiple myeloma cells to identify genes which when suppressed made cancer cells resistant to a common class of drugs called proteasome inhibitors such as bortezomib or carfilzomib. Then, the team studied bone marrow biopsies from patients to further understand their results. The process identified two genes (IRE1 and XBP1) that control response to the proteasome inhibitor and the mechanism underlying the drug resistance that is the barrier to cure.

The findings showed recurrence was due to an intrinsic resistance found in immature tumor progenitor (mother) cells is the root cause of the disease and also spawns relapse. The research demonstrates that although the visible cancer cells that make up most of the tumor are sensitive to the proteasome inhibitor drug, the underlying progenitor cells are untouched by this therapy. These progenitor cells then proliferate and mature to reboot the disease process, even in patients who appeared to be in complete remission.

“Our findings reveal a way forward toward a cure for multiple myeloma, which involves targeting both the progenitor cells and the plasma cells at the same time,” says Rodger Tiedemann, M.D., a hematologist specializing in multiple myeloma and lymphoma at Princess Margaret. “Now that we know that progenitor cells persist and lead to relapse after treatment, we can move quickly into clinical trials, measure this residual disease in patients, and attempt to target it with new drugs or with drugs that may already exist.”

“Some myeloma cells are too immature to be caught by the drugs and thus hide underground only to reemerge later,” says Keith Stewart, M.B., Ch.B., Dean for Research at Mayo Clinic in Arizona and contributor to the study. “This study has wide implications in the search for a cure of this common blood cancer as this ‘progenitor cell’ will have to be targeted.”

Jonathan Keats, Ph.D., head of TGen’s Multiple Myeloma Research Laboratory, said: “This study, which leverages data generated at TGen as part of the Multiple Myeloma Genomics Initiative, shows how mutations acquired by multiple myeloma tumors can make a tumor resistant to specific therapies and highlights the importance of TGen’s precision medicine approaches.”

Dr. Tiedemann says: “If you think of multiple myeloma as a weed, then proteasome inhibitors are like a goat that eats the mature foliage above ground, producing a remission, but doesn’t eat the roots, so that one day the weed returns.”

The study — Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma — was funded by the National Cancer Institute, Multiple Myeloma Research Foundation, Leukemla and Lymphoma Society and Canadian Cancer Society, the Arthur Macaulay Cushing Estate and The Princess Margaret Cancer Foundation.

Dr. Tiedemann is the Molly and David Bloom Chair in Multiple Myeloma Research, at the University of Toronto, Dr. Stewart is the Anna Maria and Vasek Pollack Professor of Cancer Research at Mayo Clinic. Dr. Keats is an Assistant Professor in TGen’s Integrated Cancer Genomics Division.

Make-A-Wish

Make-A-Wish Recipient Gives Back To Arizona

This past November, the Make-A-Wish Foundation of Arizona granted the chapter’s 4,000th wish to recipient Ceci Christianson. Christianson’s wish was to appear on a national morning news television program to educate the public about becoming a registered bone marrow donor, a program which saved her life. Ceci’s mission was a success. After appearing on the morning news program, the Make-a-Wish Foundation of Arizona began receiving inquiries from Valley residents about how to become a bone marrow donor.

Christianson has continued her charitable and fundraising efforts during 2012. In an effort to bring awareness to the Foundation’s mission to grant wishes to Arizona children battling life-threatening medical conditions, Christenson, along with many other Arizonans, are participating in the 2012 Walk for Wishes, presented by Go Daddy.

Go Daddy adopted Christianson’s wish as a part of its title sponsorship for the Season of Wishes campaign. The company will also be the presenting sponsor for this year’s Walk For Wishes.

“I’m so excited to be a part of the Go Daddy team and meet the individuals who helped make my dream come true,” Christianson says. “And by walking, I’m helping make another wish possible. It’s an amazing thing to be a part of.”

The Make-A-Wish Foundation of Arizona has invited walkers and runners of all ages to participate in the event, which will take place on March 3rd in Tempe. Last year, Walk For Wishes raised $139,000, enabling the Foundation to grant fifteen wishes. This year, Make-A-Wish has set a fundraising goal of $165,000.

Because of a challenge grant from the Make-A-Wish Foundation of America, Walk For Wishes participants will have the opportunity to double or even triple their donation. Donations between $500 and $999 will be doubled, and donations more than $1,000 will be tripled.

To register, please visit wishaz.kintera.org/2012walkforwishes.

The deadline for online registration is Feb. 28, 2012. Registration for the 5K Walk and 1 Mile Family Fun Walk begins at 7:30 a.m. at Kiwanis Park located at 6111 All America Way in Tempe.