Acute myeloid leukaemia at an early age: Reviewing the interaction

Abstract

Acute myeloid leukaemia (AML) in early childhood is characterised by a high frequency of recurrent genomic aberrations associated with distinct myeloid subtypes, clinical outcomes and pathogenesis. Genomic instability is the first step of pathogenic mechanism in early childhood AML. A sum of adverse events is necessary to the development of infant AML (i-AML), which includes latency of biochemical-molecular and cellular effects. Inherited genetic susceptibility associated with exposures to biotransformation substances can modulate the risk of DNA damage and it is a very important piece in the pathogenic puzzle. In this review, we have aimed to explore the chain of events in the time-points of the natural history of i-AML, which includes maternal exposures during pregnancy, the speculations about the formation of somatic mutations during foetal life and the secondary genomic aberrations associated with i-AML. The modulation of risk conferred by xenobiotic metabolism´s genes variants is the bottom line of the pathogenic process. Since we have conducted observational and molecular investigations in early childhood leukaemia, the data focused here is based on Brazilian findings with summarised results of our experience with epidemiological and molecular studies in early-age leukaemia.

Identifying childhood leukemia with an excess of hematological malignancies in first-degree relatives in Brazil

“…The familial aggregation of leukemia in siblings with somatic aberrations such as ETV6-RUNX1 , KMT2-A-r , and NOTCH1 mutations that we have previously reported (as case reports in siblings) in international collaboration and age at the time of leukemia diagnosis were significantly correlated with somatic mutations that initiate during fetal life (high hyperdiploidy, ETV6-RUNX1 , KMT2A -r, TCR -rearrangements, and NOTCH1 mutation) ( 17 , 27 – 30 ). The sibships were of the same AL subtype with concordant markers (BCP-ALL, T-ALL, and/or AML) and shared the same cytogenetic aberrations.…”

Concordant Acute Myeloblastic Leukemia in Identical Twins Treated with Allogeneic Transplantation From a Younger HLA-Identical Sibling Following a Single Apheresis Procedure

“…AML represents 20% of childhood leukemia, and has a higher incidence in infants with characteristic cytogenetic abnormalities [ 5 ]. IAML has a higher prevalence of unfavorable risk factors and an increased susceptibility to therapy-related toxicity [ 6 ].…”

A Simple-to-Use Nomogram for Predicting Survival in Children with Acute Myeloid Leukemia

“…Acute myeloid leukemia (AML) is a disease of the hematopoietic stem cells (HSC), marked by irregular development and immature blast cell proliferation in the bone marrow [1,2]. Childhood AMLs account for nearly 20% of childhood leukemia and >50% of fatalities in the aforementioned populations [3,4].…”