The Intern At Work: Internal Medicine
When the Bone Marrow Breaks Down: Primary Myelofibrosis
25 Jan 2026
What is primary myelofibrosis and how does it affect bone marrow function?
Imagine a construction site where the bricklayers and foremen are hard at work building houses. Ideally, there's an efficient system in place with supervision and safety measures to ensure that the houses are well built and up to code. But imagine things start to go wrong. Due to a lack of quality control, the construction workers start rushing, leading to excessive and incorrectly built houses.
There's too much cement being spilled all over the site, making the ground hard and unworkable. The houses, poorly built and unstable, flood the market anyway, which is obviously unsafe. Eventually, the chaos at the construction site makes for an impossible working environment, forcing construction to move to other locations.
Just like a busy construction site, our bone marrow is equally hard at work producing our red blood cells, white blood cells, and platelets. When things start to go wrong at a cellular level and the bone marrow is facing an infiltrative disease, there can be dire consequences in the blood. Today, our patient has myelofibrosis and you are the doctor.
Welcome to The Intranetwork, a podcast written by medical residents meant to serve you better on the wards and on call. Today's episode is titled, When the Bone Marrow Breaks Down, Primary Myelofibrosis. Time for a minute physiology. Our bone marrow can be thought of as a construction site responsible for producing our body's red blood cells, white blood cells, and platelets.
The bone marrow is found primarily in large bones such as our pelvis, ribs, sternum, and spine. Inside the bone marrow, hematopoietic stem cells are continuously generating new blood cells across all three cell lines. Early blood cells undergo a regulated process of maturation and differentiation before entering the bloodstream as red blood cells, white blood cells, and platelets.
Normal hematopoiesis is further supported and regulated by a complex network of proteins termed the extracellular matrix. One example of a protein in the extracellular matrix is collagen. The exact pathophysiology of primary myelofibrosis is not fully understood. 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.
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