**Question:** A 50-year-old woman has had easy fatigability and noted a dragging sensation in her abdomen for the past 5 months. Physical examination reveals that she is afebrile. She has marked splenomegaly, but no lymphadenopathy. Laboratory studies show her total WBC count is 250,000/mm3 with WBC differential count showing 64% segmented neutrophils, 11% band neutrophils, 7% metamyelocytes, 5% myelocytes, 4% myeloblasts, 3% lymphocytes, 2% basophils, 2% eosinophils, and 2% monocytes. A bone marrow biopsy is performed, and karyotypic analysis of the cells reveals a t (9;22) translocation. Medical treatment with a drug having which of the following modes of action is most likely to produce a complete remission in this patient?

A. Inhibition of protein synthesis
B. Inhibition of DNA synthesis
C. Inhibition of RNA synthesis
D. Inhibition of RNA synthesis

**Correct Answer:**

**Core Concept:** The t(9;22) translocation is a chromosomal abnormality associated with chronic myeloid leukemia (CML). It results in the fusion of the BCR and ABL genes, leading to the production of a constitutively active tyrosine kinase, known as BCR-ABL fusion protein. This protein causes abnormal proliferation of myeloid cells, leading to the characteristic features of CML.

**Why the Correct Answer is B:**

In chronic myeloid leukemia (CML), the t(9;22) translocation leads to the activation of the BCR-ABL tyrosine kinase, which results in the uncontrolled proliferation of myeloid cells. To target this abnormality, we need a drug that inhibits the activity of the BCR-ABL tyrosine kinase.

**Why the other options are incorrect:**

A) Inhibition of protein synthesis: This mode of action would target all proteins, not just the BCR-ABL tyrosine kinase. It would not be specific to the CML pathology.

C) Inhibition of RNA synthesis: Similar to option A, this mode of action would target all RNA molecules, not just the BCR-ABL mRNA.

D) Inhibition of RNA synthesis: This mode of action would target all RNA molecules, not just the BCR-ABL mRNA.

**Clinical Pearl:** In CML, treatment targeting the BCR-ABL tyrosine kinase is crucial for achieving a complete remission (CR) in CML patients. Options A, C, and D are not specific enough to target the underlying abnormality. Option B, on the other hand, is specific to the BCR-ABL tyrosine kinase, which is the key driver of CML pathogenesis.