Combination therapy shows promise for chronic myeloid leukemia

September 7, 2016, University of Texas M. D. Anderson Cancer Center

A study in mice combining two inhibitor drugs for treatment of chronic myeloid leukemia (CML) has revealed potential for not only stopping the disease completely, but also significantly lowering the cost for treatment. CML is a cancer of the white blood cells accounting for 20 percent of adult leukemia.

The study at The University of Texas MD Anderson Cancer Center was led by Michael Andreeff, M.D., professor, and Bing Carter, Ph.D., professor, both of the department of Leukemia. Findings were published in the Sept. 7 online issue of Science Translational Medicine.

Researchers combined the BCR-ABL (TKI), with another inhibitor drug known as venetoclax, and observed encouraging response and cure rates for both the chronic phase of the disease and its fatal end-stage phase called blast crisis. BCR-ABL inhibitors are the current standard-of-care treatment allowing most patients to remain in remission, but they do not entirely eradicate the cancer cells. In some patients, the cancer returns in a form that is untreatable. Approximately 100,000 patients in the U.S. are kept on life-long TKI therapy at a cost of $100,000 annually, a treatment that is unaffordable for many patients.

"Our results demonstrate that this study in mice employing combined blockade of BCL-2 and BCR-ABL has the potential for curing CML and significantly improving outcomes for patients with blast crisis, and, as such, warrants clinical testing," said Andreeff. "This combination strategy may also apply to other malignancies that depend on kinase signaling for progression and maintenance."

TKIs for CML are the most successful class of molecular targeted therapy of any malignant disease, but are not effective in eliminating CML stem cells. Since the persistent stem cells could allow the cancer to return and advance to the fatal blast crisis stage, patients must remain on the drugs for the rest of their lives.

"It is believed that TKIs do not eliminate residual stem cells because they are not dependent on BCR-ABL signaling," said Carter. "Hence cures of CML with TKIs are rare."

Carter has worked for several years on eliminating the residual CML , which could mean CML patients no longer would require expensive lifelong TKIs. Based on this study, combining TKIs with BCL-2 inhibitor, an agent pioneered by Andreeff's group for use in both acute and chronic myeloid leukemias, may be a solution.

"Long-term treatment with TKIs comes at a high cost, both in terms of side effects and financially," she said. "Worldwide, most CML patients cannot afford the extraordinary expenses associated with TKI-based therapy. And, unfortunately, for patients who progress to , there are no meaningful treatments and survival is counted in weeks or months."

Explore further: How do harmful chronic myelogenous leukemia stem cells obtain their nutrients?

More information: "Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells," Science Translational Medicine, stm.sciencemag.org/lookup/doi/ … scitranslmed.aag1180

Related Stories

How do harmful chronic myelogenous leukemia stem cells obtain their nutrients?

August 27, 2015
A research group in Japan and in Korea has found a novel nutrient uptake process that maintains the activity of murine chronic myelogenous leukemia (CML) stem cells. Pharmacological inhibition of nutrient uptake decreased ...

Study identifies new drug target in deadly form of leukemia

June 3, 2013
A research team led by the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has identified ways to inhibit the function of a key protein linked to stem cell-like behavior in terminal-stage chronic myeloid leukemia ...

Blueprint for next generation of chronic myeloid leukemia treatment

August 20, 2014
Researchers at Huntsman Cancer Institute (HCI) at the University of Utah have identified and characterized mutated forms of the gene that encodes BCR-ABL, the unregulated enzyme driving the blood cancer chronic myeloid leukemia ...

Fighting resistant blood cancer cells

June 20, 2016
Chronic myeloid leukemia (CML) develops through chromosomal alterations in blood-forming cells of the bone marrow and usually occurs in older persons. Around 20 percent of adults diagnosed with leukemia suffer from this type ...

Cell marker found for leukemia-initiating capacity in chronic myelogenous leukemia

February 16, 2016
University of Alabama at Birmingham researchers have found a marker on blood cells that may help the most pressing problem in chronic myelogenous leukemia, or CML, today—an inability to get patients off treatment.

Scientists identify drugs to target 'Achilles heel' of chronic myeloid leukaemia cells

June 9, 2016
New research, by the Universities of Glasgow and Manchester, has revealed an 'Achilles heel' of chronic myeloid leukaemia (CML) and found drugs to successfully target this weakness and eradicate the disease in mice.

Recommended for you

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.

Catching up to brain cancer: Researchers develop accurate model of how aggressive cancer cells move and spread

February 15, 2018
A brief chat at a Faculty Senate meeting put two University of Delaware researchers onto an idea that could be of great value to cancer researchers.

0 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.