WBR0488

Author	[[PageAuthor::Rim Halaby, M.D. [1], Alison Leibowitz [2] (Reviewed by Alison Leibowitz)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 51-year-old male presents to the physician's office with pruritus, which he says manifests especially following a hot shower. The patient has noticed a recent increase in the intensity of the pruritis, as well as recurrent headaches and episodes of dizziness throughout the past 3 months. Upon physical examination, the patient appears flushed with a ruddy complexion, has a blood pressure of 165/92 mmHg, and splenomegaly. Further investigation reveals significantly elevated hemoglobin at 17.4 g/dL. If the patient's condition is secondary to a genetic mutation, which of the following receptor types is most likely involved?]]
Answer A	AnswerA::Receptor tyrosine kinase
Answer A Explanation	AnswerAExp::JAK2 is not a receptor tyrosine kinase.
Answer B	AnswerB::Non-receptor tyrosine kinase
Answer B Explanation	[[AnswerBExp::Polycythemia vera manifests due to a mutation in JAK2, a non-receptor tyrosine kinase.]]
Answer C	AnswerC::G-protein coupled receptor
Answer C Explanation	AnswerCExp::JAK2 is not part of the G-protein coupled receptor.
Answer D	AnswerD::Intracellular steroid receptor
Answer D Explanation	AnswerDExp::JAK2 is not part of the intracellular steroid receptor.
Answer E	AnswerE::Ion channel-associated receptor
Answer E Explanation	AnswerEExp::JAK2 is not part of an ion channel-associated receptor.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Polycythemia vera (PV) is a myeloproliferative disorder characterized by excessive erythroid cell production. The massive increase in red blood cells leads to a higher blood viscosity, accounting for the symptoms and complications of the disease. PV manifests with pruritus, secondary to an increase in histamine, skin discoloration, gouty arthritis, and thrombotic events associated with a hypercoagulable state. The majority of patients with PV (95%) have a mutation of JAK2, a non-receptor tyrosine kinase. This mutation leads to hypersensitivity to erythropoeitin (EPO) signals and constitutive activation of EPO signaling, even in the absence of EPO, with a concomitant increase in RBC production. Treatment consists primarily of periodic phlebotomies to decrease blood viscosity and prevent complications. Educational Objective: Polycythemia vera manifests due to a mutation in JAK2 a non-receptor tyrosine kinase. References: James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. Apr 28 2005;434(7037):1144-8.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Polycythemia vera, WBRKeyword::JAK2 mutation, WBRKeyword::genetics, WBRKeyword::inheritance, WBRKeyword::lesion, WBRKeyword::dermatology, WBRKeyword::skin, WBRKeyword::arthritis, WBRKeyword::RBC, WBRKeyword::genome, WBRKeyword::abnormality
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::