RESUMO
BACKGROUND: Therapy-induced leukemia is a well-known clinical syndrome occurring as a late complication in patients treated with cytotoxic therapy. OBSERVATION: We herein present results of analysis of common gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) genes in a 10-year-old boy who developed very rare type of cancer, mixed phenotype acute leukemia, 6 years after treatment of acute lymphoblastic leukemia. CONCLUSIONS: Impairment in function of GST and MTHFR enzymes found in our patient may have contributed to the development of secondary mixed phenotype acute leukemia, although precise mechanism remains elusive.
Assuntos
Biomarcadores Tumorais/genética , Glutationa Transferase/genética , Leucemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Segunda Neoplasia Primária/genética , Polimorfismo Genético/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Doença Aguda , Criança , Citometria de Fluxo , Genótipo , Glutationa S-Transferase pi/genética , Humanos , Leucemia/tratamento farmacológico , Masculino , Segunda Neoplasia Primária/tratamento farmacológico , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Indução de RemissãoRESUMO
Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1(+) acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1(+) cells’ frequency. The bottleneck is caused by the very low body TEL-AML1(+) cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1(+) body cell count is low because TEL-AML1 fusion is generated at cell level of 10(-3) to 10(-4) just during the late fetal lymphopoiesis i.e. after the 36th gestational week.