Myelofibrosis (MF) comes under the heading of rare cancer. A recent article in Newswise, University of Utah, describes the disease as the failure of bone marrow to produce normal blood cells. It is considered to be a type of chronic leukemia.
What is Myelofibrosis?
The disease is essentially a disorder of the spongy tissue within the bone. The tissue (bone marrow) contains stem cells that are responsible for forming blood cells. Fibrous tissue (scar tissue) replaces healthy bone marrow preventing it from producing a sufficient amount of blood cells.
The bone marrow’s inability to produce a normal amount of blood cells leads to fatigue, anemia, and swelling of the spleen. MF usually occurs after age sixty with overall survival about five years post-diagnosis.
The Cause of MF
Although all the factors that cause the genetic mutations in MF are not known, researchers have associated the development of MF with blood stem cells that develop mutations in MPL, TET2, JAK2, and CALR or other genes.
These mutations (abnormal cells) create mature cells which overwhelm the bone marrow. As it becomes more difficult for the bone marrow to produce healthy blood cells, production of these cells will move to the spleen, causing inflammation, or they will move to other areas in the body. (See details here)
MF does not affect reproductive cells and is therefore seldom inherited.
Stem cell transplants have the potential to cure MF. However, the majority of MF patients have health issues that prevent them from undergoing the lengthy transplant procedure.
Currently, ruxolitinib is the drug therapy used to treat MF patients. Ruxolitinib will decrease the size of the spleen and relieve symptoms. In general, however, its effects are short-lived and it will not decrease the number of abnormal MF cells.
Other forms of therapy for MF have included blood transfusions, chemotherapy, radiation, and surgery.
As members of the Huntsman team explain, JAK inhibitors such as ruxolitinib reduce symptoms but are not curative. The Huntsman team saw a need to find other targets in MF.
During their study, the team discovered that myelofibrosis cells show a sensitivity to disruptions of the cellular process of nuclear-cytoplasmic transport (NCT) that is vital to the maintenance of normal cellular functions.
At the same time, they found that an experimental drug called Selinexor, a selective inhibitor, was being tested in several clinical trials for other types of blood cancers.
The next step was to find out if blocking the NCT process would affect the growth of the myelofibrosis cells. The researchers duplicated a mutation in mice that causes MF symptoms in humans.
The mice were given Selinexor and showed the same response as the mice that were given ruxolitinib with one significant difference. The Selinexor mice showed a reduction in malignant cells.
Relying on the results of these tests, the team Huntsman Cancer Institute designed a clinical trial that will study Selinexor and its efficacy in treating MF patients. This trial is now recruiting relapsed and refractory myelofibrosis patients with a goal of including twenty-four subjects.
Their intent is to examine Selinexor for clinical benefits and to perform close monitoring for adverse events. (see National Clinical Trial 03627403).
Positive results from this trial will lead to additional studies with increased patient participation.