What is Responsible for the Development of Myelofibrosis?

Myelofibrosis is caused by a defect in blood cells.

Myelofibrosis is a serious blood disorder in which you produce too few red blood cells, and too many white blood cells. It is caused by a defect in your bone marrow stem cells that makes them grow and proliferate out of control.

Production of Blood Cells

Myelofibrosis is a disorder of hematopoeisis, the process that makes blood cells from primitive precursors in your bone marrow called hematopoetic stem cells. The stem cells divide and differentiate into red blood cells, white blood cells and platelets.

Defect in Myelofibrosis

Myelofibrosis occurs when your bone marrow makes too few of the red blood cells that carry oxygen, causing anemia (constant fatigue and weakness) and too many white blood cells. The overproduction of white blood cells taxes the liver and spleen, which can make them grow too big.

Cause

Myelofibrosis begins with a genetic mutation in a single bone marrow stem cell. The mutation causes the affected stem cell to grow and reproduce out of control, because its replication switch is stuck in the "on" position.

Effects

The mutant stem cell grows and reproduces out of control. It makes more copies of itself, and more daughter cells that will become red and white blood cells. The mutant stem cells crowd out normal stem cells because they grow so much faster. Soon the defective stem cells take over and the proportion of mutant red and white blood cells in your circulation increases, causing symptoms.

Origin

Usually, the mutation that causes bone marrow stem cells to grow out of control is acquired during your lifetime instead of being inherited from your parents. That is why myelofibrosis mainly affects people over the age of 50, who have lived long enough for the mutation to occur randomly and then spread.

References

• MayoClinic.com: Myelofibrosis
• Lancet; "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders"; E. Joanna Baxter et al.; March, 2005
• Blood; "MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients"; Animesh D. Pardanani et al.; November 2006