Abstract 3311: The alteration in key regulator genes of autophagy is mainstream mechanism of therapy resistance and impact prognosis of acute myelogenous leukemia (AML): results from diagnosis genomic analysis on 148 consecutive patients treated with intensive chemotherapy and long-term survival follow-up

Introduction There are no clear evidences if autophagy can lead to therapy resistance or favor apoptosis in cancer; it can function as a pro-apoptotic mechanism, or it can improve stresses survival clearing damaged mitochondria and proteins accumulation. Levels and activity of pro-apoptotic and anti-apoptotic proteins, particularly bcl-2 and p53, high levels of cAMP, and a complex made by pink/park could play as fulcrum of this yin and yang effect of autophagy. Our study aims to define the role of autophagy in AML, and to establish if gain or loss in autophagy could reduce the patients’ chance to respond to induction, and to worsen OS. Methods We analyzed 148 consecutive newly diagnosed non M3 AML patients treated with induction chemotherapy regimens containing at least one dose of anthracycline. We screened all patients for TP53, FLT3, NMP1 mutations; we performed Affymetrix SNP array 6.0 or Cytoscan HD. Survival data were collected prospectively, with a median follow-up of 18 months. Results Autophagy alteration (gene group 1: ULK1 CHR11; ULK1 CHR17; BECN1; ATG14; AMBRA1; UVRAG; ATG9A; ATG9B; PIK3C3; PIK3R4) were related to lower Complete Remission rate (CR%) after induction in univariate (p