Myelofibrosis (NORD)

Definitions & Key takeaways

Myelofibrosis is a type of bone marrow disorder that affects the production of blood cells. In Myelofibrosis, the bone marrow tissue is replaced with fibrotic tissue, which interferes with blood cell production. Symptoms include anemia, fatigue, bone pain, itching, fever, and weight loss. Treatment options may include medications like ruxolitinib, bone marrow transplants, and blood transfusion.

Watch video only
Myelofibrosis is a disease in which the bone marrow gets replaced by connective tissue in a process called fibrosis. Since the bone marrow’s main role is to produce erythrocytes, or red blood cells; leukocytes, or white blood cells; and thrombocytes, or platelets, the process of fibrosis interferes with production of these cell types.
Now, many cells in the bone marrow are hematopoietic progenitors, which are precursors to the different types of blood cells.
In addition to these cells there are fibroblasts, which are connective tissue cells. Now, myelofibrosis can be primary or secondary.
Primary myelofibrosis is caused by a gene mutation within hematopoietic cells, which activates a signalling pathway called the JAK-STAT pathway.
The mutation in gene encoding the enzyme, JAK2, activates the JAK-STAT pathway to go into overdrive so that the cells begin to mature and divide rapidly, quickly filling up the bone marrow.
A large majority of these cells turn into megakaryocytes which go on to make platelets. These megakaryocytes release cytokines, which are molecules that create inflammation.
And one of these cytokines is fibroblast growth factor which activates fibroblasts. The activated fibroblasts engage in the process of fibrosis - they make lots of connective tissue that ultimately begins to fill up and scar the bone marrow and replaces hematopoietic cells.
In response, the hematopoietic cells migrate to liver, spleen, and lungs - a process called extramedullary hematopoiesis.
These tissues enlarge and sometimes become dysfunctional. The extramedullary hematopoiesis is often not able to fully compensate for the loss of bone marrow hematopoiesis, and it can lead to a shortage of all blood cell lines - called pancytopenia.
Secondary myelofibrosis can develop from conditions like essential thrombocythemia, which is where excess platelets are produced, and polycythemia vera, which is where excess red blood cells are produced.
Common symptoms of myelofibrosis are bone pain, fatigue, itching, fever, and weight loss. Sometimes the extramedullary hematopoiesis can lead to hepatomegaly, splenomegaly, and pulmonary hypertension.
In addition, the anemia can lead to fatigue, and the low white cell count - the leukopenia - can lead to frequent infections.
The excess platelets can lead to thrombotic complications like deep vein thrombosis and pulmonary thromboembolisms. In myelofibrosis there’s typically an initial increase in blood cells - particularly platelets, but eventually those levels drop and there’s pancytopenia.
A blood smear will show abnormal teardrop shaped red blood cells, immature nucleated red blood cells, and immature white blood cells and platelets.
Bone marrow biopsy can show an increase in hematopoietic cell numbers in early myelofibrosis or a decrease in hematopoietic cell numbers and fibrosis later in the process.
Erythropoietin can be given for anemia, and blood transfusion can be given for pancytopenia. The medication ruxolitinib can help inhibit the JAK-STAT pathway, and relieves symptoms and specifically causes a reduction in spleen size.
Alternatively, a hematopoietic stem cell transplantation, which comes with its own risks, can be done to potentially cure myelofibrosis in some individuals.
All right, as a quick recap myelofibrosis is a rare bone marrow disorder, where the bone marrow tissue is replaced with fibrotic tissue, and that interferes with blood cell production.
Blood tests and bone marrow biopsy are crucial for diagnosis. It can be treated with hematopoietic stem cell transplantation and ruxolitinib.