General AML|TP53

AACR 2017: Poster 3311/14 – Impact of autophagy alterations in AML

On Tuesday 4th April, at the 107th American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, there was a poster session focused on “Autophagy and Cancer”. During this session, a poster (3311/14) titled “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” by Giovanni Marconi from the Institute of Hematology, Bologna, Italy and colleagues was on display.

Marconi et al. aimed to clarify the role of autophagy and its impact in therapy response and survival outcomes in 148 newly diagnosed Acute Myeloid Leukemia (AML) patients (median age = 56 years) treated with induction chemotherapy regimens. Patients were divided into 3 groups based on alterations in gene pathways; group 1 (autophagy gene alterations), group 2 (AMP-activated Protein Kinase [AMPK] pathway gene alterations) and group 3 (alterations in genes involved in the switch from a physiological role of autophagy to a resiliency mechanism).

 The key results were:
  • Alterations in group 1 were associated with lower Complete Remission (CR) % after induction; P < 0.001
  • Alterations in group 1 significantly led to a worse Overall Survival (OS, P < 0.001) and was associated with complex karyotype and TP53 mutations (P < 0.001)
  • Significant differences were observed in terms of survival independently both in gain and loss in group 1 genes, P < 0.001
  • Alterations in group 2 and group 3 were associated with worse OS; P < 0.001
  • Alterations in group 2 and group 3 were associated with lower CR % after induction; P < 0.001

The authors highlighted that their study is the first to use a “genomic approach” to identify the role of autophagy in AML. They further concluded by stating that “gain and loss in autophagy key regulator genes are associated with poor prognosis and therapy resistance” in AML.  

References
  1. Marconi G. et al. 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 [ Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [3311/14].