Acute promyelocytic leukemia (APL): a review of the literature

Abstract

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.

The Role of ARHGAP9: Clinical Implication and Potential Function in Acute Myeloid Leukemia

“…Our study showed the differently expressed genes associated with ARHGAP19 expression were enriched in APL. While 95% of APL is the abnormalities of t (15;17) which encoded the PML-RARA fusion protein [52]. What is more, the expression of ARHGAP9 is the lowest in t(15;17) AML compared with the other chromosome abnormalities in AML, and all patients with t (15;17) were in the ARHGAP9 low group in our study.…”

Differentiation Syndrome, a Side Effect From the Therapy of Acute Promyelocytic Leukemia

“…Management for DS has remained more-or-less unchanged throughout the years. Prophylactic corticosteroids are generally used in patients with APML on therapy with ATRA to prevent DS [ 2 ]. Although their benefit is not fully understood, it can still be considered.…”

“…Promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) protein results in a blockade in the differentiation of leukemic cells at the promyelocytic stage [ 1 ]. Individuals diagnosed with APML are recommended to immediately start all-trans retinoic acid (ATRA), arsenic trioxide, and chemotherapy to prevent the coagulopathy that can be detrimental [ 2 ]. Differentiation syndrome (DS), also known as Retinoic Acid Syndrome, is a life-threatening complication that can occur in patients with APML that are undergoing therapy with ATRA or arsenic [ 3 ].…”

TYRO3 Truncation Resulting From a t(10;15)(p11;q15) Chromosomal Translocation in Pediatric Acute Myeloid Leukemia

“…Because chromosome abnormalities acquired by the leukemic cells have been shown to be remarkable diagnostic and prognostic parameters (9-11), the cytogenetic examination of bone marrow cells is now an indispensable component of the clinical management of patients with hematological malignancies, including AML. Sometimes, cytogenetic information is decisive in the choice of optimal treatment for AML-patients as illustrated by the finding at diagnosis of the chromosomal translocation t(15;17)(q24;q11), the hallmark of acute promyelocytic leukemia (APL), which is treated and monitored differently from other AML subtypes (12)(13)(14).…”