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What causes PV?

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PV is a disease that occurs because of an acquired mutation that affects a specific enzyme called the JAK2 enzyme. This enzyme is responsible for transmitting signal transduction from the receptor of the cytokines into the nucleus via the JAK-STAT pathway, and under normal circumstances, the JAK2 enzyme is extremely important for hematopoiesis because without it, no signal transduction can take place and no myeloproliferation can happen.

No one knows why the mutation happens, but this mutation causes this enzyme to be uninhibited. Under normal conditions, binding of the cytokines to the specific growth receptor triggers this phosphorylation of JAK2 and then which in turn sends the signal through the STAT pathway to the nucleus driving on cellular production.

Ultimately once the production is done, it shuts off, but in cases of PV, and because of the mutation, it escapes inhibition basically by unknown mechanism, so then you end up with uncontrolled myeloproliferation. So it's easy to understand why patients end up with such high white count, high platelet count, and hematocrits when they have this activated JAK2 mutation.

Image of Jamile M Shammo, MD, FASCP, FACP
Jamile M Shammo, MD, FASCP, FACP Associate Professor Rush University Medical Center | Chicago, IL
As principal investigator of clinical trials in her area of expertise, Dr Shammo is heavily involved in education, research, and administrative activities in the Division of Hematology/Oncology. She is recognized nationally for her expertise in bone marrow failure syndromes/paroxysmal nocturnal hemoglobinuria (PNH) and was chosen to serve as a national coordinator for the US PNH registry.