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Adenosine Monophosphate Activated Protein Kinase (AMPK) enhances chemotherapy response in Acute Myeloid Leukemia

Lais Ghiraldeli1, Rebecca Anderson1, Kristin Pladna1

  • 1Section on Hematology and Oncology, Comprehensive Cancer Center of Atrium Health Wake Forest Baptist, USA.

Cancer Letters
|March 24, 2022
PubMed

Insights

Adenosine monophosphate activated protein kinase (AMPK) regulates cell metabolism and impacts cancer. In acute myeloid leukemia (AML), AMPK activation sensitizes cancer cells to chemotherapy, improving patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Adenosine monophosphate activated protein kinase (AMPK) is a key regulator of cellular metabolism.
  • AMPK's role in cancer is complex, acting as both a tumor suppressor and a resistance factor.
  • Its specific function in acute myeloid leukemia (AML) chemotherapy response is not well understood.

Purpose of the Study:

  • To investigate the role of AMPK in the response of acute myeloid leukemia (AML) cells to chemotherapy.
  • To determine if AMPK influences chemotherapy resistance or sensitivity in AML.

Main Methods:

  • Generated AML cell lines lacking AMPK activity (knockout cells).
  • Assessed chemotherapy response (cytarabine, doxorubicin) in vitro and in vivo.
  • Analyzed DNA damage response markers (γH2AX, p53, p21) and apoptosis.
  • Examined TCGA datasets for correlations between AMPK subunit PRKAA1 expression and patient survival.
  • Utilized AICAR, an AMPK activator, to test sensitization effects.

Main Results:

  • AMPK knockout AML cells exhibited significant resistance to cytarabine and doxorubicin.
  • Mitochondrial mass and function remained unchanged in AMPK knockout cells.
  • AMPK deficiency led to a diminished DNA damage response and reduced apoptosis post-chemotherapy.
  • Low PRKAA1 expression in AML patients correlated with significantly shorter survival.
  • AICAR treatment sensitized AML cells to chemotherapy.

Conclusions:

  • AMPK plays a crucial role in sensitizing acute myeloid leukemia cells to chemotherapy.
  • The cellular metabolic state, regulated by AMPK, influences cell fate decisions and therapeutic response in AML.
  • Targeting AMPK may represent a viable strategy to enhance chemotherapy efficacy in AML treatment.

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