Dr. Ayesha Warsi

However, there are some hallmark features.

Myelofibrosis is considered a clonal myeloproliferative neoplasm wherein progenitor hematopoietic stem cells acquire mutations in JAK2, CalR, or NPL.

These mutations result in overactivation of the JAK-STAT signaling pathway.

This abnormal signaling triggers excessive proliferation of myeloid cells, especially megakaryocytes.

Excessive proliferation characterizes the early hyperproliferative stage of myelofibrosis.

Hyperproliferation can also impact the extracellular matrix.

Increased megakaryocyte proliferation stimulates fibroblasts to overproduce collagen through greater secretion of cytokines, such as growth factor beta and thrombopoietin.

Over time, this can lead to fibrosis of the bone marrow.

As fibrosis worsens with disease progression, the bone marrow loses its ability to produce normal blood cells.

Bone marrow failure characterizes the later stages of primary myelofibrosis, resulting in cytopenias.

To help compensate for the loss of normal bone marrow production, hematopoiesis is shifted to other sites in the body.

This is known as extramedullary hematopoiesis and mainly impacts the liver and spleen, but can occur in almost any organ.

In terms of disease classification, myelofibrosis is classified as a myeloproliferative neoplasm.

Primary myelofibrosis occurs de novo without a preceding disorder.

Secondary myelofibrosis develops as a complication of polycythemia vera or essential thrombocythemia, two other chronic myeloproliferative neoplasms.

These other myeloproliferative neoplasms are often associated with similar mutations, such as in JAK2, Cal-R, or NPL, but begin with overproduction of red blood cells in polycythemia vera or overproduction of platelets in essential thrombocythemia before progressing to secondary myelofibrosis.

Inflammatory cytokines and certain mutations drive the progression of polycythemia vera and essential thrombocythemia to secondary myelofibrosis.

Primary myelofibrosis occurs mainly in older adults, with a median age at presentation of 67.

Of note, approximately 10% of patients are diagnosed under the age of 45.

It is the least common of the chronic myeloproliferative neoplasm disorders, with an estimated annual incidence of 0.2 to 0.5 per 100,000 persons per year.