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Return to Researchers Target Myelodysplastic Syndromes Overview

More on Researchers Target Myelodysplastic Syndromes

Researchers Target Myelodysplastic Syndromes

Lack of red blood cells, white blood cells, and platelets result in anemia, infections, bleeding, and bruising. About one-third develop myelogenous leukemia.

New York (Nov 18, 2010)

Illustration of red blood cells
Illustration of red blood cells

Azra Raza, M.D., balances a microscope slide between her fingers, fogs it with her breath, and holds it up to the light. Eight small cloudy rectangles are revealed and disappear as the condensation dissipates. Each miniature snapshot could hold the secret to what causes the disease to which she has dedicated the last 30 years of her professional life: myelodysplastic syndromes (M.D.S.).

"See that? Those are the complete genomes of eight people with M.D.S.," she explains. She's almost certain there is a pathogenic cause for M.D.S., perhaps a virus, and that the application of modern sequencing techniques to study such genomes could identify it.

About M.D.S.

M.D.S. is a group of diseases in which the body does not make enough red blood cells, white blood cells, and blood-clotting platelets. About a third of patients with M.D.S. develop a cancer called acute myelogenous leukemia. Patients often first develop anemia due to low red blood cell counts; they may also become more prone to infections and bleed or bruise easily. The diagnosis of M.D.S. is made using blood tests, and is then confirmed by biopsying the bone marrow.

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Each of the NewYork-Presbyterian campuses has been designated by the M.D.S. Foundation, Inc. as a Center of Excellence for the research, diagnosis, and treatment of the disease. Patients with M.D.S. come from all over the country to seek care.

Because M.D.S. is a disease that is most common in older individuals, it is expected to rise in incidence as the population ages. "M.D.S. is becoming to older patients what prostate cancer is to elderly men – meaning that if you live long enough, you're bound to experience some lowering of your blood counts," says Dr. Raza, who directs the M.D.S. Program at NewYork-Presbyterian/Columbia University Medical Center.

Azra Raza, M.D.
Azra Raza, M.D.

Gail Roboz, M.D., who leads the M.D.S. program at NewYork-Presbyterian/Weill Cornell Medical Center, notes that low blood counts are commonly dismissed as a normal part of aging, when in fact they may be M.D.S. "If there are abnormal blood counts, than there needs to be an explanation," she says. "It's important to order the right tests and determine the cause so that the appropriate treatment can begin sooner."

Hospital's Collaborative Approach

The Hospital's pathologists work with the doctors to diagnose blood disorders such as M.D.S. "We can't overestimate the value of having a correct diagnosis of M.D.S.," adds Dr. Roboz. "It's important to get it right to determine if patients might benefit from standard treatments or if we need to pursue investigational approaches." The molecular profile of each patient's disease is examined to predict how aggressive the illness might be, and whether they need treatment soon or if they can wait.

No Cure, But Treatment

There is no cure for M.D.S., but there are treatments to relieve symptoms and extend life. Patients initially receive drugs to boost their blood cell counts, such as epoietin alfa (Procrit®) for red blood cells. If the M.D.S. does not respond well to this treatment, patients need blood transfusions once or twice a month for life. Transfusions that might only be performed on an inpatient basis at some community hospitals can be done at NewYork-Presbyterian on an outpatient basis – thanks to the multidisciplinary support team of an academic medical center, the sophisticated facilities, and a strong blood supply.

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The effectiveness of thalidomide has been established in patients with M.D.S. Today its chemical cousin, lenalidomide (Revlimid®), is a commonly prescribed capsule that was developed based on the findings of Dr. Raza's investigations. Azacitidine (Vindaza®) and decitabine (Dacogen®) are two other drugs also prescribed for M.D.S. – azacitidine is given by injection and decitabine is given intravenously (by vein). These new drugs, which were approved for M.D.S. in the last decade, have improved the outlook for patients diagnosed with the disease.

Gail J. Roboz, M.D.
Gail J. Roboz, M.D.

The drugs must be taken for life, however. "There's no doubt that while these treatments are advances, they're still not good enough," says Dr. Roboz. "They represent a step forward, but they are not a home run."

Some patients benefit from hematopoietic stem cell transplantation, in which they receive healthy bone marrow stem cells from a donor to repopulate their own diseased bone marrow after they have received high doses of chemotherapy to wipe it out. But patients over age 55 – the bulk of M.D.S. patients – cannot tolerate this treatment. M.D.S. researchers are therefore seeking to cure the disease at its roots.

M.D.S. starts when one abnormal stem cell in the bone marrow divides more rapidly than the others, filling the marrow with dysfunctional cells and causing the normal stem cells to become dormant. Dr. Azra's research showed that a protein called tumor necrosis factor-alpha (TNFα) makes this single rogue stem cell divide and multiply, while also promoting the death of mature bone marrow cells. That's why inhibitors of TNFα, such as thalidomide and lenalidomide, work against M.D.S.

But not all M.D.S. patients respond to those drugs, because at the molecular level, M.D.S. is not one type of disease. "If we want to cure this disease, we have to find and kill that one aberrant stem cell," explains Dr. Raza.

Looking Forward

NewYork-Presbyterian/Columbia's basic science and clinical research programs for patients with M.D.S. feature a strongly collaborative effort between experienced laboratory scientists and clinicians. Dr. Raza is intrigued by the potential anticancer effects of spices such as ginger and turmeric – natural TNFα inhibitors – on M.D.S. outcome. She is seeking funding for clinical trials to evaluate these supplements.

She is also determined to find a germ causing M.D.S., such as a virus. Technology to detect evidence of such a virus in the genes of M.D.S. patients is still evolving, and Dr. Raza hopes to be able to use her tissue bank of some 50,000 samples to pinpoint the culprit.

At NewYork-Presbyterian/Weill Cornell, researchers are evaluating new drugs and new combinations of existing drugs for M.D.S. One study is evaluating an oral version of the chemotherapy drug clofarabine (which is used in its intravenous form to treat leukemia in children), while another is assessing lenalidomide in combination with an immune-suppressing drug called cyclosporine.

NewYork-Presbyterian researchers benefit from the bidirectional flow of information between the lab and the clinic. "My inspiration comes from the bedside. All of our questions come from the bedside," Dr. Azra explains. "This research is like a blank canvas that we've all been putting strokes on for years. As the picture continues to come together, it will be revolutionary."

Contributing faculty for this article:

Azra Raza, M.D. is the Director of the Myelodysplastic Syndromes Center at NewYork-Presbyterian/Columbia University Medical Center and a Professor of Medicine at Columbia University College of Physicians and Surgeons.

Gail Roboz, M.D. is an Associate Attending Physician at NewYork-Presbyterian/Weill Cornell Medical Center and an Associate Professor of Medicine at Weill Cornell Medical College.

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