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Leukemia Research: Primary Myelofibrosis

Rekha Rao Manepalli in lab.

October 07, 2019

Bone marrow makes more than 200 billion blood cells every day, including red blood cells, platelets and white blood cells. Each of these play an important role in our overall health:

  • Red blood cells carry oxygen to tissues in the body.
  • Platelets help blood to clot in order to stop bleeding and reduce bruising.
  • White blood cells fight and prevent infections.

Located in the innermost part of our bones, bone marrow is soft and spongy with blood vessels running through to let nutrients and waste in and out. It’s the perfect environment for blood cells to divide and mature.

But what happens when the bone marrow’s environment changes?

Primary myelofibrosis, a type of chronic leukemia, is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous, scar-like material.

“The bone marrow becomes brittle, forcing the blood cells to leave their home in order to survive,” says Rekha Rao Manepalli, PhD, researcher at The University of Kansas Cancer Center. “The blood cells go to other organs such as the spleen, liver and even brain. Then they start dividing.”

If the cells travel to the spleen, for example, the organ can become enlarged and compress the spine. Furthermore, with the disruption of normal blood cell production, patients experience exhaustion, weakness, easy bruising and bleeding, fever and bone pain.

Because it’s a chronic disease, the issue can last for years.

Dr. Manepalli has been studying this disease and other forms of leukemia for 9 years. She notes that the current treatments for primary myelofibrosis only address the symptoms, not the disease itself.

Why not, Dr. Manepalli suggests, treat the cells that actually produce the disease complication, fibrosis?

“It’s a symbiotic relationship between the leukemia stem cell and the bone marrow; they are each helping the other survive. Let’s target the environment in which the leukemia grows and end that relationship,” Dr. Manepalli says.

Dr. Manepalli and her team are studying a specific gene that plays an important role in the development of fibrous bone marrow. This particular gene “turns on” the production of collagen, the culprit for brittle bone marrow. In patient samples with primary myelofibrosis, there is significant expression of this gene in the microenvironment.

Her team hypothesizes that the bone marrow stroma, i.e., microenvironment, is responsive to something that induces this collagen-producing gene. If that can be stopped, perhaps leukemia can also be inhibited.

In her lab, Dr. Manepalli discovered that by reducing the expression of the gene, collagen production slows. To test this, she exposed a healthy cell to 2 different sets of plasma samples: 1 from a patient with primary myelofibrosis, the other from a healthy person.

“The plasma from the patient had so much more collagen surrounding the cells, but the healthy patient did not," she explains. "So, the patient’s plasma is doing something to the cell to induce collagen production."

This theory will also be tested on mouse models in the future. The ultimate hope is that Dr. Manepalli and her team can identify a method to help bone marrow return to its original state and reverse the fibrosis.

“We’re tracing the pathology of primary myelofibrosis," she says. "It takes time and patience but we are very encouraged by our findings so far."

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