The present project is aimed at giving more insight on the role played by some players of nuclear inositide cycle, namely PI-PLCbeta1 and PI3-K in the growth of AML balsts and at establishing if the deletion of PI-PLCbeta1 gene is a reliable marker for MDS progression to AML. The rationale is mainly based on the fact that till now there is no reliable marker to establish if MDS patients with normal karyotype could rapidly and lethally evolove to AML. MDS evolves in AML in about 30% of cases after variable intervals from diagnosis; the clinical transition is demonstrated by the clonal proliferation of the hematopoietic precursor that generates leukemic blasts unable to differentiate. It is considered that the evolution to AML is associated with additional genetic changes acquired by MDS patients. Moreover AML rising as the evolution of MDS is much less responsive to chemotherapeutic agents than is the de novo AML. Approximately half of MDS patients have a detectable chromosome abnormality and those patients are usually thought to be at higher risk for developing AML than MDS patients having normal karyotype. It has recently been observed that the clinical follow-up of these patients is not sufficient since some of them (15 to 20%) have surprisingly worse and poorer clinical outcome than expected. This group of patients is the one that has not a satisfying management and approach as no markers, which could allow a more accurate prognosis, have been identified. Therefore it seems of great interest to detect prognostic elements to add to the karyotype in MDS, in order to screen higher risk patients. Our preliminary observation hint at the deletion of PI-PLCbeta1 gene as a potential, reliable and easy to detect the high risk group of MDS patients. Therefore the aim of this project is to demonstrate that the monoallelic deletion of PIPLCbeta1 gene can be used as a novel and highly trustworthy tool to discriminate between MDS patients with normal karyotype and the high risk ones, as well as the key role of this key signaling molecule, involved in the control of checkpoints of cell cycle, in the pathophysiology of AML. In addition the role of PI3-K/Akt pathway related to PI-PLC, will be clarified in the proliferation of MDS blasts.
L. Cocco (2006). Nuclear phospholipase C and cancer.
Nuclear phospholipase C and cancer
COCCO, LUCIO ILDEBRANDO
2006
Abstract
The present project is aimed at giving more insight on the role played by some players of nuclear inositide cycle, namely PI-PLCbeta1 and PI3-K in the growth of AML balsts and at establishing if the deletion of PI-PLCbeta1 gene is a reliable marker for MDS progression to AML. The rationale is mainly based on the fact that till now there is no reliable marker to establish if MDS patients with normal karyotype could rapidly and lethally evolove to AML. MDS evolves in AML in about 30% of cases after variable intervals from diagnosis; the clinical transition is demonstrated by the clonal proliferation of the hematopoietic precursor that generates leukemic blasts unable to differentiate. It is considered that the evolution to AML is associated with additional genetic changes acquired by MDS patients. Moreover AML rising as the evolution of MDS is much less responsive to chemotherapeutic agents than is the de novo AML. Approximately half of MDS patients have a detectable chromosome abnormality and those patients are usually thought to be at higher risk for developing AML than MDS patients having normal karyotype. It has recently been observed that the clinical follow-up of these patients is not sufficient since some of them (15 to 20%) have surprisingly worse and poorer clinical outcome than expected. This group of patients is the one that has not a satisfying management and approach as no markers, which could allow a more accurate prognosis, have been identified. Therefore it seems of great interest to detect prognostic elements to add to the karyotype in MDS, in order to screen higher risk patients. Our preliminary observation hint at the deletion of PI-PLCbeta1 gene as a potential, reliable and easy to detect the high risk group of MDS patients. Therefore the aim of this project is to demonstrate that the monoallelic deletion of PIPLCbeta1 gene can be used as a novel and highly trustworthy tool to discriminate between MDS patients with normal karyotype and the high risk ones, as well as the key role of this key signaling molecule, involved in the control of checkpoints of cell cycle, in the pathophysiology of AML. In addition the role of PI3-K/Akt pathway related to PI-PLC, will be clarified in the proliferation of MDS blasts.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
