By: Diana Barnes-Brown for Medtech1Researchers at the M.D. Anderson Cancer Center at the University of Texas recently shared some illuminating findings on the role of molecular pathways in acute myelogenous leukemia (also known as acute myeloblastic leukemia or AML), the most common form of leukemia.
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Risk factors for AML:
Gender (men develop AML more frequently than women
Smoking
Past radiation or chemotherapy treatment
Past treatment for childhood leukemia
Exposure to atomic bomb radiation
Exposure to the chemical benzene
A history of myelodysplastic syndrome or similar blood disorders
Call your doctor if you notice any of the following signs and symptoms of AML:
Tiredness or exhaustion
Fever
Easy bruising
Failure to stop bleeding after even small cuts and scrapes, frequent nose bleeds, other bleeding disorders
Tiny, flat reddish speckles on the skin (known as petechiae)
Weight loss
Loss of appetite |
AML is a fast-growing cancer of the blood and bone marrow, in which the bone marrow manufactures many underdeveloped white blood cells. White blood cells are key players in immune functioning: they fight infection and defend the body against unwanted intruders. In AML, the “unfinished” white blood cells replace normal white blood cells and crowd out normal white and red blood cells and platelets that are vital to survival. This process leads, respectively, to compromised immune systems, severe anemia, and bleeding disorders, which can rapidly kill a patient if not aggressively treated. Chemotherapy and bone marrow transplants have been the traditional, and often the only, lines of defense against the disease, and though they often bring patients to states of remission, AML tends to return. The University of Texas research team, led by Steve Kornblau, M.D., an associate professor in the Department of Blood and Marrow Transplantation, reported their findings in an October issue of the medical journal Blood. The team studied bone marrow and blood samples from 188 adults suffering from AML, and followed their battles with the disease in order to monitor the long-term effects of three molecular pathways that act to signal cells in the disease. Together, the pathways create a domino-like effect that allows the disease to wreak havoc on the body.
The researchers found that patients in whom none of the molecular chain reactions were active had a median survival time of 78.6 weeks. For those who had one active pathway that number dropped to 57.9 weeks; two active pathways further lowered the number to 42.3 weeks; with three, patients’ survival time dropped to 23.4 weeks.
Further, the pathways seem to cooperate with one another, which explains why in patients with even one active pathway, survival time drops dramatically. “Targeting just one of these pathways won’t be effective because we also found that they cross-activate each other, they essentially cover for each other,” noted Kornblau.
This discovery poses new challenges to cancer researchers, in part because new cancer drugs are tested in controlled settings – that is, one at a time – so it will be difficult to invent the combinations or gain the approvals needed to test a drug or drugs that act on the trifecta rather than on only one of the pathways. Because they create and market competing products, pharmaceutical companies can be resistant to the type of collaborative work and cooperative testing that would best identify multi-drug therapies, which might only be possible by combining the best efforts of many corporations in the cancer treatment industry.
A related editorial in the same issue of Blood noted that co-active and cooperative pathways that essentially fill in for one another are not at all unusual in cancer. "This compensatory ability suggests that the use of single "targeted" agents may be suboptimal, a concept that, unfortunately is all too well supported by clinical experience in all malignancies and has broad implications for the entire field of cancer therapeutics," said Judith Karp, M.D., of Johns Hopkins University. She urged that physicians and others involved in the development of successful treatments “listen carefully to the authors' eloquent plea for a new paradigm in drug development.”
Needless to say, those whose lives are impacted by this deadly form of cancer are anxious to learn of any new treatment that might increase survival rates. Roughly 20 percent of patients with AML recover after chemotherapy, and bone marrow transplants recover about 30 percent of the time.
