[1] It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow.
In PMF, the bony aspects of bone marrow are remodeled in a process called osteosclerosis; in addition, fibroblasts secrete collagen and reticulin proteins that are collectively referred to as fibrosis.
Patients with myelofibrosis have an increased risk of acute meyloid leukemia and frank bone marrow failure.
The V617F subsustition also renders hematopoietic cells more sensitive to growth factors that use JAK2 for signal transduction, which include erythropoietin and thrombopoietin.
[8] The MPL gene codes for a protein that acts as a receptor for thrombopoietin, a growth factor that enhances production of platelets.
[citation needed] In primary myelofibrosis, progressive scarring, or fibrosis, of the bone marrow occurs, for the reasons outlined above.
Another complication of extramedullary hematopoiesis is poikilocytosis, or the presence of abnormally shaped red blood cells.
[citation needed] Myelofibrosis can be a late complication of other myeloproliferative disorders, such as polycythemia vera, and less commonly, essential thrombocythemia.
In these cases, myelofibrosis occurs as a result of somatic evolution of the abnormal hematopoietic stem cell clone that caused the original disorder.
[22] Splenectomy is sometimes considered as a treatment option for patients with myelofibrosis in whom massive splenomegaly is contributing to anaemia because of hypersplenism, particularly if they have a heavy requirement for blood transfusions.
[23] In November 2011, the US Food and Drug Administration (FDA) approved ruxolitinib (Jakafi) as a treatment for intermediate or high-risk myelofibrosis.
[28] In August 2019, the FDA approved fedratinib (Inrebic) as a treatment for adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).
[29] In March 2022, the FDA approved pacritinib (Vonjo) with an indication to treat adults who have intermediate or high-risk primary or secondary myelofibrosis and who have platelet (blood clotting cells) levels below 50,000/μL.
In 2016, the WHO revised their classification of myeloproliferative neoplasms to define Prefibrotic primary myelofibrosis as a distinct clinical entity from overt PMF.