Acute leukemia in early childhood

Abstract

Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL /AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months) has detected TEL /AML1 +ve (N = 9), E2A/PBX1 +ve (N = 4), PML /RARA +ve (N = 4), and AML1/ETO +ve (N = 2) cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07), OR = 2.27 (95%CI = 1.56-3.31) and OR = 9.08 (95%CI = 2.95-27.96)], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

Molecular and chromosomal mutations among children with B-lineage lymphoblastic leukemia in Brazil’s Federal District

“…The frequency of transcript BCR/ABL p190 in 2007 (3.03%) was similar to that in the literature (Rubnitz and Look, 1999;Abdelhaleem, 2007;Sastre et al, 2007). On the other hand, although potentially a random event, the values obtained for E2A/PBX1 fusion in 2006 (8.70%) and 2007 (9.68%) were above the median reported, above the existing data in Brazil (Emerenciano et al, 2007) and among the highest ever registered (Jimenéz-Morales, 2008).…”

“…The presence of genetic rearrangements involving the MLL gene seems to be correlated to the non-expression of CD10 and immunophenotype pro-B, and is inversely associated with age, occurring at a higher frequency (50 to 80%) among children younger than one year (Pui et al, 1990;van Dongen et al, 1999;Emerenciano et al, 2007). In the group studied, there were two cases of unweaned infants with this characterization.…”

“…The recurrent rearrangements associated with poor prognosis occur at a lower frequency: t(1;19) E2A/PBX1, present in 5 to 6% of cases (van Dongen et al, 1999;Raimond, 1999); p190 type t(9;22) BCR/ABL, in 3 to 5% (Raimond, 1999;Sastre et al, 2007), and t(4;11) MLL/AF4, detected in 2 to 5% of pediatric B-ALL cases (Pui et al, 1990;van Dongen et al, 1999) and in over 50 to 85% of B-ALL cases among unweaned infants (van Dongen et al, 1999;Emerenciano et al, 2007).…”

Mutation Screening and Association Study of the Folylpolyglutamate Synthetase (FPGS) Gene with Susceptibility to Childhood Acute Lymphoblastic Leukemia

“…Several risk factors have been shown to affect the risk of childhood acute lymphoblastic leukemia (Buffler et al, 2005;Emerenciano et al, 2007;Inaba and Mulligha, 2013) and a complex interplay between inherited genetic background and specific environmental exposures are most likely to determine ALL susceptibility (de Jonge et al, 2009;Yang et al, 2010). Genetic polymorphisms in genes involving in folate metabolic pathway are putative candidate modulators of ALL susceptibility (Thirumaran et al, 2005;Karathanasis and Kalmanti, 2009;Koppen and Kaspers, 2010;Yang et al, 2011).…”

Multilocus Association of Genetic Variants in MLL, CREBBP, EP300, and TOP2A with Childhood Acute Lymphoblastic Leukemia in Hispanics from Texas

“…No biological factors have been identified which account for this difference in risks among different ethnic or racially defined populations. Substantial evidence exists indicating that several risk factors (including gender, age, ethnicity, exposure to radiation, genetic syndromes) are involved in increased risk of ALL (5)(6)(7)(8)(9). Hispanic children with ALL have been found to have a higher incidence rate for secondary or therapy-related acute myeloid leukemia (t-AML) after treatment with topoisomerase II (topo II) inhibitors (10).…”