Acute Promyelocytic Leukemia in Children and Adolescents

Abstract

Acute promyelocytic leukemia (APL) is a rare subtype of AML characterized by a reciprocal balanced translocation between chromosomes 15 and 17 that fuses the PML gene with the RARα gene and leads to the leukemic phenotype. Although best described in large clinical trials of adults, APL, like other forms of AML, also occurs in children. The positive outcome of children with APL mirrors the dramatic increase in survival seen in adults since the introduction of all-trans retinoic acid (ATRA). In this paper, we review the diagnosis of APL in children as well as large, retrospective, clinical trial data collected on pediatric APL. We also raise management issues and toxicities that are unique to children.

MST-312 induces G2/M cell cycle arrest and apoptosis in APL cells through inhibition of telomerase activity and suppression of NF-κB pathway

“…The PML-RARα fusion gene plays a central role in leukemogenesis, including arrest of differentiation and evasion of apoptosis [1,2]. One of the most important hallmarks of tumor cells is deregulation of signaling pathways that contribute to tumor formation and progression as well as tumor resistance to chemotherapeutic agents.…”

Treatment Outcome and the Genetic Characteristics of Acute Promyelocytic Leukemia in Children in Poland From 2005 to 2018

“…Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia (AML). In most cases, it is characterized by translocation (15;17) with the PML-RARA fusion gene (1)(2)(3), but about 1-2% of APL cases are due to rare variant translocations including ZBTB16/RARA, NMP/RARA, NUMA/RARA, STAT5B/RARA, PRKAR1a/RARA, BCOR/RARA, and FIP1L1/RARA (4)(5)(6). APL comprises about 5-10% of pediatric AML (1) and about 0.4% of all malignancies in children.…”

“…Methods of the treatment used in children are based on clinical studies performed on greater adult population. Until the late 1980's, APL was the most lethal subtype of AML (2,3). The result of the treatment improved significantly since the 1980's when specific treatment with all-trans retinoic acid (ATRA) was introduced (2, 3, 7-9).…”

“…Use of the specific treatment in APL allowed reduction of the chemotherapy especially cumulative anthracycline doses (13,(15)(16)(17). The main causes of the treatment failure are still early deaths, mostly in the course of intracranial hemorrhage (2,3,18). In the large analysis comprising 683 patients from different international studies, initial high WBC counts and obesity were found as likely predictors of thrombohemorrhagic early deaths in childhood APL (18).…”

Genetic network profiles associated with established resistance to ionizing radiation in acute promyelocytic leukemia cells and their extracellular vesicles

“…However, although rare, repeated exposure to ionizing radiation (IR) can produce other leukemic cells and/or radio-resistant leukemic cells and thus presents an obstacle to treatment against treatment (4,5). Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), characterized by a block at the promyelocytic stage of hematopoiesis (6,7).…”