Review Question - QID 106506

Acute promyelocytic leukemia (APML) is caused by a translocation of the retinoic acid receptor alpha (RARA) gene from chromosome 17 to chromosome 15, which results in the PML/RARA fusion gene.

Acute promyelocytic leukemia is a cancer of the body's white blood cells which results in accumulation of immature granulocytes called promyelocytes. APML is a subtype of acute myelogenous leukemia (AML). The signs and symptoms of APML include fatigue, weakness, dyspnea, and thrombocytopenia. To diagnose APML a bone marrow aspirate or biopsy is performed. The classic cytogenetic abnormality detected in APML is t(15;17)(q22;q12), a translocation that fuses the RARA gene with a nuclear regulatory factor gene on 15q22 (PML gene). Currently, first line treatment for APML is all-trans retinoic acid, the acid form of vitamin A.

Luo et al. examined the effect of small interference RNA (siRNA) targeting PML-RARa mRNA on the activity of the acute promyelocytic leukemia. They found that the cell growth of siRNA treated group was inhibited, and the apoptosis of that cell line could be induced. Thus, the siRNA targeting PML-RARalpha mRNA might be a valid therapy of acute promyelocytic leukemia.

De Braekeleer et al. review the cellular effects and consequences of the PML-RARA fusion gene in APML. They describe that RARA fusion proteins behave as potent transcriptional repressors of retinoic acid signaling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of ATRA or arsenic trioxide.

Incorrect Answers:
Answer 1: The t(8;14) translocation is characteristic of Burkitt's lymphoma which creates a cMYC/IGH fusion protein
Answer 2: The t(9;22) translocation is characteristic of chronic myelogenous leukemia (CML), not APML. It does however, create the BCR/ABl1 fusion gene.
Answer 4: The t(14;18) translocation is characteristic of follicular lymphoma which creates an IGH/Bcl-2 fusion gene.
Answer 5: The t(9;22) translocation is characteristic of chronic myelogenous leukemia (CML) which creates the BCR/ABl1 fusion gene.