Acute promyelocytic leukemia (APL): a review of the literature
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Joaquin J. Jimenez1,2, Ravinder S. Chale1,2, Andrea C. Abad1 and Andrew V. Schally3,4,5,6,7
1 Dr. Phillip Frost Department of Dermatology, Miller School of Medicine, University of Miami, Miami, FL, USA
2 Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA
3 Division of Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA
4 Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, Miami, FL, USA
5 Department of Medicine, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA
6 Division of Hematology Oncology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA
7 Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA
|Joaquin J. Jimenez,||email:||[email protected]|
Keywords: promyelocytic leukemia; arsenic trioxide; retinoic acid; resistance
Received: December 19, 2019 Accepted: February 17, 2020 Published: March 17, 2020
Acute Promyelocytic Leukemia (APL) is characterized by a block in differentiation where leukemic cells are halted at the promyelocyte stage. A characteristic balanced chromosomal translocation between chromosomes 15 and 17 t (15;17) (q24; q21) is seen in 95% of cases — the translocation results in the formation of the PML-RARA fusion protein. The introduction of retinoic acid (RA) and arsenic trioxide (ATO) has been responsible for initially remarkable cure rates. However, relapsed APL, particularly in the high-risk subset of patients, remains an important clinical problem. In addition, despite the success of ATRA & ATO, many clinicians still elect to use cytotoxic chemotherapy in the treatment of APL. Patients who become resistant to ATO have an increased risk of mortality. The probability of relapse is significantly higher in the high-risk subset of patients undergoing treatment for APL; overall approximately 10-20% of APL patients relapse regardless of their risk stratification. Furthermore, 20-25% of patients undergoing treatment will develop differentiation syndrome, a common side effect of differentiation agents. Recent evidence using in vitro models has shown that mutations in the B2 domain of the PML protein, mediate arsenic resistance. Alternative agents and approaches considering these clinical outcomes are needed to address ATO resistance as well as the relapse rate in high risk APL.
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