Each week, Osmosis shares a USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case involves a 68-year-old man. Polymerase chain reaction testing reveals a mutation in a gene encoding for a non-receptor tyrosine kinase. Can you figure it out?
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?
A. Fanconi anemia
B. Chronic myeloid leukemia
C. Follicular lymphoma
D. Polycythemia vera
E. Acute myeloid leukemia
Scroll down to find the answer!
→ Reinforce your understanding with more self-assessment items on Osmosis.
The correct answer to today’s USMLE® Step 1 Question is…
D. Polycythemia vera
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
A. Fanconi anemia
Incorrect:Fanconi anemia is caused by defects in homologous DNA recombination. Patients with this congenital condition present at a young age with pancytopenia, short stature, microcephaly, and cafe-au-lait spots. In contrast, defects in homologous DNA recombination play no role in the pathogenesis of this patient’s condition (primary myelofibrosis).
B. Chronic myeloid leukemia
Incorrect: Chronic myeloid leukemia (CML) is caused by a translocation between chromosomes 9 and 22. This results in fusion of the BCR and ABL gene, producing a tyrosine kinase with increased activity. However, the JAK2 gene mutation responsible for this patient’s condition plays no role in the pathogenesis of CML.
C. Follicular lymphoma
Incorrect: Follicular lymphoma is caused by a mutation in the gene encoding the Bcl-2 protein. Normally Bcl-2 keeps the mitochondrial membrane intact and prevents apoptosis. The mutation results in overexpression of Bcl-2, which prevents apoptosis and causes uncontrolled cellular proliferation. In contrast, this patient has primary myelofibrosis, which is most often secondary to a mutation in the JAK2 gene.
E. Acute myeloid leukemia
Incorrect: Acute myeloid leukemia (AML) is caused by a translocation between chromosomes 15 and 17. This disrupts the retinoic acid receptor (RAR), which is needed for myeloblast maturation. As a result, there is proliferation of myeloblasts, the unipotent stem cells that can differentiate into neutrophils, eosinophils, basophils, and monocytes. However, the JAK2 gene mutation responsible for this patient’s condition plays no role in AML.
Main Explanation
This patient has primary myelofibrosis, which is one of the myeloproliferative disorders. These are a group of blood disorders characterized by the excess proliferation of cells of myeloid lineage. The four high-yield myeloproliferative disorders are: polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myeloid leukemia. The first three conditions are most often caused by a Janus Kinase 2 (JAK2) gene mutation. CML is caused by a t[9;22] chromosomal translocation.
Primary myelofibrosis is characterized by the uncontrolled proliferation of megakaryocytes and scar tissue deposition. Over time, the hematopoietic stem cells residing in the bone marrow are crowded out by scar tissue. This results in pancytopenia and a “dry tap” on bone marrow biopsy. This pancytopenia results in reduced production of red blood cells (anemia), platelets (increased bleeding) and white blood cells (increased infections). Some of the stem cells migrate to other organs (e.g., liver, spleen) and proliferate there. This is termed extramedullary hematopoiesis and may cause hepatosplenomegaly. The enlarged spleen and liver can compress the stomach, ultimately resulting in decreased appetite/weight loss.
Major Takeaway
Myeloproliferative disorders are characterized by the excess proliferation of cells of myeloid lineage. They are often caused by a JAK2 gene mutation. The four high-yield myeloproliferative disorders are: polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myeloid leukemia.
References
George, T.I., Arber, D.A. (2018) Atlas of bone marrow pathology. Springer New York. ISBN: 978-1-4939-7469-6.
Meier, B., Burton, J.H. (2014) Myeloproliferative disorders. Emergency Medicine Clinics of North America. 32(3), 597-612. Doi: 10.1016/j.emc.2014.04.014.
Tefferi, A. (2018) Primary myelofibrosis: 2019 update and diagnosis, risk-stratification and management. American Journal of Hematology. 93(12), 1551-1560. Doi: 10.102/ajh.25230.
_________________________
Want more USMLE® Step 1 practice questions? Try Osmosis today! Access your free trial and find out why millions of current and future clinicians and caregivers love learning with us.
The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB.
Leave a Reply