WBR0163

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Author PageAuthor::William J Gibson
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology
Sub Category SubCategory::Hematology, SubCategory::Oncology
Prompt [[Prompt::A 45 year old man presents to his primary care physician for fatigue and weight loss of 10 pounds over the past month. On physical exam, the spleen is palpable 7 cm below the costal margin and several bruises are observed across the body. Laboratory testing is significant for an elevated white blood cell count and reduced platelet count. Bone marrow biopsy demonstrates hyperplastic granulocytes which are positive for a t(9;22) translocation. The patient is started on an inhibitor to the fusion gene produced by this translocation. This drug would be expected to have activity in which of the following tumors?]]
Answer A AnswerA::Breast cancer
Answer A Explanation AnswerAExp::'''Incorrect:''' Breast cancer is not currently treated with tyrosine kinase inhibitors. HER2 positive breast cancers can be treated with trastuzamab.
Answer B AnswerB::Gastrointestinal stromal tumor
Answer B Explanation AnswerBExp::'''Correct:''' Gastrointestinal stromal tumors commonly have mutations in the c-Kit tyrosine kinase. Imatnib is also able to block the kinase activity of the mutated c-Kit.
Answer C AnswerC::Hepatocellular carcinoma
Answer C Explanation AnswerCExp::'''Incorrect:''' Hepatocellular carcinoma is not treated with imatinib. HCC is often secondary to viral hepatitis or cirrhosis and may be treated with surgery or other interventional techniques.
Answer D AnswerD::Mantle cell lymphoma
Answer D Explanation AnswerDExp::'''Incorrect:''' Mantle cell lymphoma is a rare non-Hodgkin’s lymphoma that affects elderly males. It is not susceptible to imatinib therapy.
Answer E AnswerE::MALT Lymphoma
Answer E Explanation AnswerEExp::'''Incorrect:''' MALT Lymphoma is associated with H Pylori infection and is not susceptible to imatinib therapy. For localized MALT Lymphoma, treatment of underlying H. Pylori infection is often sufficient to induce tumor regression.
Right Answer RightAnswer::B
Explanation [[Explanation::The patient in this vignette has chronic myelogenous leukemia, caused by the BCR-ABL translocation between chromosomes 9 and 22. This translocation causes a novel tyrosine kinase to be formed that can constitutively transmit cell growth signals in affected cells. Imatinib blocks the action of this new gene product and thereby starves the tumor cells of the mitogenic signals upon which they rely to survive. Imatinib can also be used to treat gastrointestinal stromal tumors (GISTs) as its kinase blocking activity is not entirely specific to the BCR-ABL gene product. 85% of GISTs have activating mutations of the c-kit gene, which can be inhibited by imatinib.

Educational Objective: Imatinib, a tyrosine kinase inhibitor, can be used to treat both CML and GISTs.

References: First Aid 2012 page 393.
Educational Objective:
References: ]]

Approved Approved::Yes
Keyword WBRKeyword::Cancer, WBRKeyword::Chemotherapy, WBRKeyword::Leukemia, WBRKeyword::Imatinib, WBRKeyword::CML, WBRKeyword::Chronic myelogenous leukemia, WBRKeyword::GIST, WBRKeyword::Gastrointestinal stromal tumor
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