Vacuolar ATPase as a possible therapeutic target in human acute myeloid leukemia

ABSTRACT

Introduction: V-ATPase is a proton pump expressed both in the membrane of intracellular organelles (e.g. endosomes, lysosomes, Golgi structures) and the plasma membrane. It is an important regulator of organellar functions, intracellular molecular trafficking, intercellular communication and intracellular signaling. It is therefore considered as a possible therapeutic target in the treatment of human malignancies.

Areas covered: Relevant publications were identified through literature searches in the PubMed database. We searched for original articles and reviews describing the possible importance of V-ATPase for leukemogenesis and chemosensitivity in human myeloid cells, especially acute myeloid leukemia (AML) cells.

Expert commentary: The expression of V-ATPase in the primary human AML cells varies between patients, and high levels are associated with high constitutive release of a wide range of soluble mediators. Several of the molecules included in the V-ATPase interactome may also be important in leukemogenesis and/or development of chemoresistance in human AML. Therapeutic targeting of V-ATPase should therefore be regarded as a possible therapeutic strategy in human AML, but the efficiency of such targeting will probably differ between patients. The possibility of toxicity, especially hematological toxicity and immunosuppression, also has to be clarified.

KEYWORDS:

• V-ATPase
• acute myeloid leukemia
• cytokine
• chemokine
• apoptosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors receive financial support for their scientific work from the Norwegian Cancer Society, the Western Norway Regional Health Authority and University of Bergen.