Aetiology of childhood leukemia

Abstract

Leukemia is the most common cancer to affect children, accounting for approximately a third of all childhood cancers. The major morphological subtypes of leukemia, acute lymphoblastic leukemia (ALL), and acute myeloblastic leukemia (AML), are characterized by chromosomal translocations involving over 200 genes including mixed lineage leukemia (MLL), TEL, and AML1. Chromosomal translocations involving the MLL gene at 11q23 are a common feature of infant acute leukemia, found in up to 80% of all cases, and there is strong evidence that rearrangements involving the MLL gene or the TEL-AML1 gene fusion can originate in utero. As with most other cancers, the mechanism by which leukemia arises is likely to involve gene-environment interactions. Accordingly, it is important to identify exposures that cause DNA damage and induce chromosome breaks which are inadequately repaired, ultimately leading to the initiation and disease progression. Exposures acting before birth and early in life has long been thought to be important determinants of leukemia, and the list of suspected chemical, physical, and biological agents continues to increase. Unfortunately, the evidence regarding the majority of suggested exposures is limited and often contradictory, and there are areas, which clearly warrant further investigation in order to further our understanding of the aetiology of childhood leukemia.

The Sensitivity of Children to Electromagnetic Fields

“…16 Subtypes of AML and ALL are frequently characterized by genetic alterations, including changes in chromosome number (hyperdiploidy or hypodiploidy) and chromosomal translocations that may involve chimeric or fusion genes. 17,18 These genes include MLL, TEL, and AML1, all of which can fuse with many other genes and, in the case of TEL and AML1, with each other. There is strong evidence that this rearrangement may originate in utero, supported by data obtained from studies of identical twins or children with concordant ALL.…”

BEMS, WHO, and the precautionary principle

“…Can you imagine a review on mechanism of interaction with biological tissue [Challis, 2005] that does not include the latest studies on interaction of RF with DNA? A recurring theme of the symposium was the possibility of cancer, and cancer was clearly linked to DNA in the good review by Lightfoot [2005]. Why not include ELF mechanisms, since cellphones include both ELF and RF, and both activate the same biological mechanisms [Blank and Goodman, 2004]?…”

Polimorfismos genéticos, susceptibilidade e resposta ao tratamento em crianças portadoras de leucemia linfoblástica aguda

“…O clone maligno que sofre a transformação pode ser tanto uma célula pluripotente como uma célula progenitora mais madura (Lightfoot T., 2005;Kebriaei et al, 2003). Aberrações na proliferação e na diferenciação dessas células são comuns e torna a hematopoiese normal comprometida.…”

“…A translocação t(9,22) (cromossomo Philadelfia), resultante da fusão BCR-ABL é encontrada em aproximadamente 5% das crianças com LLA e está associada a um prognóstico desfavorável, assim como a translocação t(4;11) (q21,23), que pode ser observada em cerca de 3% das LLAs em crianças, principalmente nos lactentes (Raynaud et al, 1996;Pui et al, 2002;Pui et al, 2003). Outras translocações que podem estar envolvidas são: t(8;14), t(2;8) e t(8;22) (envolvem o proto-oncogene MYCC) e também a t(11;14) com ponto de quebra no cromossomo 14 no locus α/δ do gene TCR, representando a translocação mais freqüente entre as LLAs de linhagem T da infância ( Privitera et al, 1992;Pui, 1995;Margolin;Poplack, 1997;Pui et al, 2004;Lightfoot, 2005). O tratamento utilizado para a LLA é a quimioterapia e a sobrevida livre de eventos por mais de cinco anos é considerada o critério de cura.…”

“…Diversos mecanismos de ação de agentes endógenos e exógenos já foram identificados e a exposição materna a substâncias tóxicas ou carcinogênicas, podem causar danos permanentes (Lightfoot, 2005). Além disso, Greaves (1993) propôs que a maioria dos casos de LLA infantil é conseqüência de respostas imunológicas anormais a infecções comuns, precedidas por um evento de mutação inicial no útero.…”