Regulação da fosfatase CDC25C do ciclo celular na leucemia aguda
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As duplica��es internas em tandem do gene do recetor FLT3 (FLT3-ITD) encontram-se em cerca de 30% dos doentes com leucemia mieloide aguda (LMA). Este oncogene influencia v�rias fun��es das c�lulas da LMA e conduz a uma prolifera��o descontrolada. Clinicamente, a FLT3-ITD est� associada a um mau progn�stico em doentes com LMA. Neste estudo, foi investigada a influ�ncia do FLT3-ITD na fosfatase CDC25C, que, como regulador do ciclo celular, influencia significativamente o controlo da divis�o celular. As experi�ncias aqui descritas mostraram que a CDC25C � fosforilada pela FLT3-ITD e activada de forma descontrolada. No modelo de c�lulas de leucemia, foi demonstrado um efeito principalmente protetor do CDC25C na presen�a de stress oncog�nico. As c�lulas geneticamente n�o intactas foram cada vez mais impedidas de se dividirem pelo CDC25C. No entanto, a presen�a simult�nea da muta��o FLT3-ITD resultou na perda desta fun��o protetora. O significado do mecanismo aqui descrito reside, portanto, no controlo da resposta da c�lula leuc�mica a danos no ADN. No entanto, o CDC25C n�o tem uma fun��o oncog�nica no sentido cl�ssico.
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