Research team uncovers root cause of multiple 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 to identify genes which when suppressed made 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 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 at the same time," says Rodger Tiedemann, M.D., a specializing in multiple myeloma and lymphoma at Princess Margaret. "Now that we know that persist and lead to relapse after treatment, we can move quickly into clinical trials, measure this 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."

More information: Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma, Cancer Cell, 2013.

add to favorites email to friend print save as pdf

Related Stories

Towards more effective treatment for multiple myeloma

Jan 09, 2012

A new study from SUNY Downstate Medical Center in Brooklyn, New York, shows that MAL3-101, a recently developed inhibitor of the heat shock protein 70 (Hsp70), appears to have potent anti-tumor effects on multiple myeloma, ...

Possible new therapy for the treatment of myeloma

Sep 05, 2012

(Medical Xpress)—Research from Karolinska Institutet shows that sorafenib, a drug used for advanced cancer of the kidneys and liver, could also be effective against multiple myeloma. The disease is one of the more common ...

Recommended for you

Immune checkpoint inhibitors may work in brain cancers

Nov 21, 2014

New evidence that immune checkpoint inhibitors may work in glioblastoma and brain metastases was presented today by Dr Anna Sophie Berghoff at the ESMO Symposium on Immuno-Oncology 2014 in Geneva, Switzerland.

New model of follow up for breast cancer patients

Nov 21, 2014

Public health researchers from the University of Adelaide have evaluated international breast cancer guidelines, finding that there is potential to improve surveillance of breast cancer survivors from both a patient and health ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.