Question

A patient is diagnosed with AML M3. Which chromosomal translocation is characteristically associated with this condition?

• A. t(9;22)
• B. t(8;21)
• C. t(15;17)
• D. t(11;14)

Hint:

AML M3 or APL = t(15;17) and PML-RARA fusion.

Answer 1

The Correct Option is C

Step 1: Understanding the Question:
The question asks for the specific cytogenetic abnormality that defines Acute Promyelocytic Leukemia (APL), which is classified as the M3 subtype in the French-American-British (FAB) system.
Step 2: Detailed Explanation:

Pathogenesis: Acute Promyelocytic Leukemia (AML-M3) is characterized by a reciprocal translocation between chromosomes 15 and 17, denoted as t(15;17)(q22;q12). This results in the fusion of the Promyelocytic Leukemia (PML) gene on chromosome 15 with the Retinoic Acid Receptor Alpha (RARA) gene on chromosome 17.

Molecular Impact: The resulting PML-RARA fusion protein acts as a dominant negative repressor of transcription. It binds to retinoic acid response elements with higher affinity than the normal receptor, blocking the differentiation of myeloid cells at the promyelocyte stage.

Clinical Significance: AML-M3 is considered a medical emergency due to its high association with severe coagulopathy and Disseminated Intravascular Coagulation (DIC). The malignant promyelocytes contain numerous primary granules (Auer rods) that, when released, trigger the coagulation cascade.

Targeted Therapy: This translocation makes AML-M3 uniquely sensitive to All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide. ATRA binds to the fusion protein, inducing the degradation of the PML-RARA repressor and allowing the promyelocytes to differentiate into mature neutrophils.

Differential Translocations: t(9;22) is the Philadelphia chromosome seen in CML and some ALL. t(8;21) is seen in AML-M2 (AML with maturation). t(11;14) is characteristic of Mantle Cell Lymphoma.

Step 3: Final Answer:
The characteristic translocation for AML-M3 (APL) is t(15;17), which creates the PML-RARA fusion gene.