Dos Santos Cédric, Récher Christian, Demur Cécile, Payrastre Bernard
Inserm U563, CPTP, IFR30, Département d'oncogenèse et signalisation dans les cellules hématopoïétiques, 31024 Toulouse.
Bull Cancer. 2006 May;93(5):445-7.
Despite important progress in the therapy of acute myeloid leukaemia (AML) most patients relapse and die from the disease, underlying the need for potent and more specific drugs for the treatment of this pathology. Recently, we demonstrated that the PI3-kinase-Akt-mTOR (mammalian target of rapamycin) pathway is constitutively activated in about 60% of AML patients cells. In vitro, low doses of the specific inhibitor of mTOR, rapamycin, block the phosphorylation of the classical targets of this kinase and inhibit the proliferation of leukemic progenitors without affecting the growth of normal haematopoietic progenitors. The results of this preclinical study led us to investigate the activity of rapamycin in relapsed, refractory, or poor-risk AML patients. The results of this study will be discussed in the review.
尽管急性髓系白血病(AML)治疗取得了重要进展,但大多数患者仍会复发并死于该疾病,这凸显了需要强效且更具特异性的药物来治疗这种病症。最近,我们证明PI3激酶 - Akt - mTOR(雷帕霉素的哺乳动物靶点)通路在约60%的AML患者细胞中持续激活。在体外,低剂量的mTOR特异性抑制剂雷帕霉素可阻断该激酶经典靶点的磷酸化,并抑制白血病祖细胞的增殖,而不影响正常造血祖细胞的生长。这项临床前研究的结果促使我们研究雷帕霉素在复发、难治或高危AML患者中的活性。本研究结果将在综述中进行讨论。