Abstract
Although the outcome has improved over the past decades, due to improved supportive care, a better understanding of risk factors, and intensified chemotherapy, pediatric acute myeloid leukemia remains a life-threatening disease, and overall survival (OS) remains near 70%. According to French-American-British (FAB) classification, AML is divided into eight subtypes (M0–M7), and each is characterized by a different pathogenesis and response to treatment. However, the curability of AML is due to the intensification of standard chemotherapy, more precise risk classification, improvements in supportive care, and the use of minimal residual disease to monitor response to therapy. The treatment of childhood AML continues to be based primarily on intensive, conventional chemotherapy. Therefore, it is essential to identify new, more precise molecules that are targeted to the specific abnormalities of each leukemia subtype. Here, we review abnormalities that are potential therapeutic targets for the treatment of AML in the pediatric population.
Highlights
Non-random chromosomal aberration t(8;21)(q22;q22) is one of the best-known mutations; it usually correlates with the acute myeloid leukemia (AML) M2 subtype and results in RUNX1::RUNX1T1 fusion gene formation, which was one of the first fusion genes to be used for minimal residual disease (MRD) monitoring [65]. t(8;21) occurs in approximately 10–12% of childhood
Translocation t(15;17)(q24.1;q21.2) resulting in PML::RARA fusion gene formation is the most common mutation driving the development of acute promyelocytic leukemia (APL), which is classified as FAB-M3 AML [15,90]
There are two distinct abnormalities important for pediatric AML that are related to translocation between 16 and 21 chromosomes: t(16;21)(p11;q22) and t(16;21)(q24;q22), which produce fusion proteins FUS::ERG and RUNX1::CBFA2T3, respectively. t(16;21)(p11; q22) occurs in about 0.4%, and the second one in 0.2% of pediatric AML cases; prognosis prediction is complicated, but the I-BFM Study Group indicated that the prognosis for FUS::ERG is poor with 4-year event free survival (EFS) of 7%, and outcome for RUNX1::CBFA2T3 is significantly better with 4-year EFS of 77% [20,21]
Summary
Acute myeloid leukemia (AML) is a relatively rare heterogeneous group of hematologic malignancies in children, but it causes disproportionate mortality [1]. Despite the fact that outcome has improved over the past decades due to improved supportive care, a better understanding of risk factors, and intensified chemotherapy, pediatric. The curability of AML is due to the intensification of standard chemotherapy, more precise risk classification, improvements in supportive care, and the use of minimal residual disease to monitor response to therapy. Chemotherapy offers a good chance of recovery in acute promyelocytic leukemia and in a form with specific favorable molecular features. In other forms of acute myeloid leukemia (AML), the cure rate with chemotherapy alone is very low (10–15%). Due to the high proportion of patients with unfavorable prognostic factors, the treatment results in the entire group of unfavorable AML risk are still poor. Recent research shows potential for on-target/off-tumor immunotherapeutic toxicity due to target antigen expression on non-malignant cells [8]
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