DHFR 19-bp insertion/deletion polymorphism and MTHFR C677T in adult acute lymphoblastic leukaemia: Is the risk reduction due to intracellular folate unbalancing?.
Gemmati, Donato 1*; De Mattei, Monica 2; Catozzi, Linda 1; Porta, Matteo Della 3; Serino, Maria L. 1; Ambrosio, Cristina 1; Cuneo, Antonio 1; Friso, Simonetta 4; Krampera, Mauro 5; Orioli, Elisa 1; Zeri, Giulia 1; Ongaro, Alessia 2
[Letter]
American Journal Of Hematology.
84(8):526-529, August 2009.
(Format: HTML, PDF)
: Folate and its derivatives are pivotal for cell cycle and proliferation. They facilitate the crosstalk between DNA synthesis and methylation crucial processes in cancer establishment [ 1]. Dietary folate or supplements (e.g., folic acid) must be fully reduced by dihydrofolate reductase (DHFR) before entering cell metabolism [ 1]. DHFR is responsible for dihydrofolate (DHF) to tetrahydrofolate (THF) conversion, as well as for assisting the generation of additional partially reduced folates (i.e., methylene-THF and formyl-THF), which are then transformed into the fully active folate (i.e., methyl-THF) with the help of methyle-netetrahydrofolate reductase (MTHFR). As the main folate isoforms involved in DNA synthesis and methylation are handled by these two key enzymes, alterations in DHFR and/or in MTHFR functions may have detrimental effects on DNA stability and cancer susceptibility [ 2-5].
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