Myelofibrosis is a serious disorder of your bone marrow, which produces your blood cells, ultimately causing severe anaemia and enlarged organs. Although myelofibrosis is caused by a genetic defect, the defect usually is not inherited from your parents but occurs during your lifetime.
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Myelofibrosis occurs when your body makes too few of the red blood cells that carry oxygen, and too many of the white blood cells that fight infections. The lack of red blood cells causes anaemia (constant fatigue and weakness) and the overproduction of white blood cells taxes the liver and spleen, often causing them to grow too large.
Myelofibrosis begins with a mutation of a gene that causes a single bone marrow stem cell to grow and reproduce out of control. Bone marrow stem cells replicate and differentiate into red blood cells, white blood cells, and platelets (for clotting). When one stem cell mutates, it passes its mutation to all of its "daughter cells." The gradual accumulation of mutant cells causes the symptoms of myelofibrosis.
Dr. Joanna Baxter reported in the March 2005 issue of Lancet that a change in a single letter of the genetic code of a gene called JAK2 causes up to 50 per cent of all cases of myelofibrosis. Mutations in a gene called MPL515 account for another 5 per cent of myelofibrosis cases, according to Dr. Animesh Pardanani in the November 2006 issue of Blood.
Drs. Baxter and Pardanani found that the products of JAK2 and MPL515 work in the same pathway controlling stem cell growth. The mutations that cause myelofibrosis jam the pathway in the "on" position so that stem cells to grow and reproduce themselves out of control.
The gene mutations that cause myelofibrosis usually are not inherited, but occur during your lifetime. That is why myelofibrosis occurs most often in people over the age of 50, who have lived long enough for the mutation to occur and then spread, causing the symptoms.
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