In:
La Pediatria Medica e Chirurgica, PAGEPress Publications, Vol. 37, No. 2 ( 2015-11-24)
Abstract:
TEL-AML1 (ETV6-RUNX1) fusion gene which is formed prenatally in 1% of the newborns, is a common genetic abnormality in childhood Bcell precursor acute lymphoblastic leukemia. But only one child out of a hundred children born with this fusion gene develops leukemia (bottleneck phenomenon) later in its life, if contracts the second mutation. In other words, out of a hundred children born with TEL-AML1 only one child is at risk for leukemia development, which means that TEL-AML1 fusion gene is not sufficient for overt leukemia. There is a stringent requirement for a second genetic abnormality for leukemia development and this is the real or the ultimate cause of the leukemia 〈 em 〉 bottleneck 〈 /em 〉 phenomenon. In most cases of TEL-AML1 〈 sup 〉 + 〈 /sup 〉 leukemia, the translocation t(12;21) is complemented with the loss of the normal TEL gene, not involved in the translocation, on the contralateral 12p. The loss of the normal TEL gene, 〈 em 〉 i.e. 〈 /em 〉 loss of heterozygosity at 12p, occurs postnatally during the mitotic proliferation of TEL-AML1 〈 sup 〉 + 〈 /sup 〉 cell in the mitotic crossing over process. Mitotic crossing over is a very rare event with a frequency rate of 10 〈 sup 〉 –6 〈 /sup 〉 in a 10 kb region. The exploration and identification of the environmental exposure(s) that cause(s) proliferation of the TELAML1 〈 sup 〉 + 〈 /sup 〉 cell in which approximately 10 〈 sup 〉 6 〈 /sup 〉 mitoses are generated to cause 12p loss of heterozygosity, 〈 em 〉 i.e. 〈 /em 〉 TEL gene deletion, may contribute to the introduction of preventive measures for leukemia.
Type of Medium:
Online Resource
ISSN:
2420-7748
,
0391-5387
DOI:
10.4081/pmc.2015.112
Language:
Unknown
Publisher:
PAGEPress Publications
Publication Date:
2015
detail.hit.zdb_id:
2850646-7
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