Myelofibrosis – causes, symptoms, diagnosis, treatment, pathology

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.