USMLE® Step 1 style questions USMLE
A 68-year-old male comes to his provider’s office for evaluation of fatigue, weakness, and 8 kg (17.6 lb) unintentional weight loss over the past 2 months. Moreover, the patient reports feeling bloated after eating small quantities of food during this same time period. His past medical history is notable for hypertension, and the patient is currently taking hydrochlorothiazide. Physical exam reveals oral mucosal pallor. Cardiac and pulmonary exams are non-contributory. Abdominal exam reveals hepatosplenomegaly. Laboratory testing results are as follows:
Laboratory value Result Hemoglobin 9.5 g/dL Hematocrit 28.5% Leukocytes 2,700/mm3 Platelets 100,000/mm3
Biopsy of the bone marrow biopsy shows increased fibrosis and reduced cell count. Polymerase chain reaction testing reveals a mutation in a gene encoding for a non-receptor tyrosine kinase. Which of the following diseases is also caused by an identical mutation?
Myelofibrosis (NORD) exam links
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Evan Debevec-McKenney, Stefan Stoisavljevic, MD
Myelofibrosis is a disease in which the bone marrow within a bone 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, normally, the vast majority of bone marrow is made of hematopoietic cells which are the early progenitor cells that can differentiate into other cell types.
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 set of enzymes that together are called the JAK-STAT pathway.
The mutation specifically causes the enzymes in 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.
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.