General AML,   DNMT3A,  IDH1/2,  NPM1,  TP53

AACR 2017: Poster 515/1 – PI3P and cAMP pathway alterations in AML patients

A poster session titled “Oncogenic Growth Factors and Signal Transducers” took place at the 107th American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA on Sunday 3rd April.

Uncontrolled activation of genes involved in the Phosphatidylinositol 3-Phosphate (PI3P) pathway via PI3K/AKT/mTOR are associated with oncogenic activity and poor survival.1 Additionally, dysregulation of AMP-Activated Protein Kinase (AMPK), a regulator of cell homeostasis, has been reported to play a role in Acute Myeloid Leukemia (AML).2

Mariachiara Abbenante from the University of Bologna, Bologna, Italy, and colleagues investigated the effect of PI3P and AMPK pathways in AML. In total, 208 newly diagnosed AML patients were screened for TP53, FLT3, NPMI, IDH1, IDH2, and DNMTA mutations.

The key results were:
  • Alterations in the P13K/AKT/mTOR pathway and AMPK pathway reported in 48% of patients (103/209)
  • Overall Survival (OS) was significantly worse in patients with alterations in the P13K/AKT/mTOR pathway compared to unaltered patients; P = 0.035
  • OS was significantly worse in patients with alterations in the AMPK pathway compared to unaltered patients; P < 0.001
  • Lower percentage of Complete Remission (CR) was associated with alterations of regulators in cyclic AMP (cAMP [increases the activity of AMPK]) pathway; P < 0.001
  • TP53 mutations, age, secondary AML, and karyotype were significantly associated with alterations of regulators in cAMP; P = 0.009

In summation, alterations in the PI3P and cAMP pathways are associated with poor prognosis in AML patients. Moreover, alterations in the cAMP pathway is associated with therapy resistance in AML.

  1. Abbenante M. et al. Alterations in phosphatidylinositol 3-phosphate (PI3P) pathway and cAMP pathway confirm poor prognosis and reduced overall survival (OS) in a series of 209 acute myeloid leukemia patients [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 [515/1].
  2. Sujobert P. & Tamburini J. Co-activation of AMPK and mTORC1 as a new therapeutic option for acute myeloid leukemia. Mol Cell Oncol. 2016 Jul; 3(4): e1071303. DOI: 1080/23723556.2015.1071303. Epub 2015 Aug 27.
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