A 67 year-old female presents with fatigue and marked splenomegaly. After further workup, a bone marrow biopsy is performed, and cytogenetic analysis of the aspirate reveals a Jak-2 mutation. Her blood smear is shown here.
What is the most likely diagnosis?
A. Chronic myelofibrosis
B. Chronic myeloid leukemia
C. Hairy cell leukemia
D. Metastatic breast carcinoma
E. Renal cell carcinoma
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(Scroll down for the answer)
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The diagnosis in this case is chronic myelofibrosis. The teardrop-shaped red cells and normoblast in this blood smear are indicative of a fibrotic marrow. While other tumors can cause a myelophthisic process, JAK-2 mutations are seen most frequently in three chronic myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and chronic myelofibrosis. Jak-2 mutations are particularly characteristic of polycythemia vera – but given the markedly enlarged spleen and extramedullary hematopoiesis in this case, chronic myelofibrosis is a better guess (not to mention that polycythemia vera wasn’t one of the choices.).
The naming of the Jak-2 protein is kind of interesting. One early meaning of Jak was “Just Another Kinase” (at the time, it seemed like just one more kinase in a long line of newly-discovered kinases). However, Jak also stands for Janus kinase, which is a clever and satisfyingly appropriate name for this kinase. Janus was the Roman God of doorways, often shown with two faces looking in opposite directions. JAK has two domains that work in opposite directions too (one domain has kinase activity, and the other domain negatively regulates the first)! Nice naming job.
Un post molto interessante. Complimenti alla professoressa Krafts.
Francesco Venuti
Grazie molto Francesco! Apprezzo i vostri commenti. (I hope that’s right!)
reson for naming of jak2 seems to be quite interesting..
reason for naming of jak2 seems to be quite interesting..
The pancytopenia in this patient rules out Polycythemia as a diagnosis. The dicovery and naming of JAK was ingenious.Thanks alot. Keep the good work.
JAK-2 mutation is a guiding hint in conditions of myeloproliferative disorders.
Great post…grazie
Fantastic page, love the cases!
I have learnt so much from here. this site gives me so much joy and knowledge. I am a Veterinary Pathologist but have gained immensely from what you teach here. i can never thank you enough. i have read your books too. How i wish i could get hard copies of them. thank you so much for being the amazing awesome teacher you are!