Perspectives of proteomics in acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a frequent hematological malignancy. Despite enormous therapeutic efforts that range from various cytotoxic agents to allogeneic stem cell transplantation, overall survival of patients with AML remains unsatisfying. The poor survival rates are mainly due to therapy-related mortality, failure of induction chemotherapy and early relapses. Therefore, novel therapeutic agents that are more efficient and better tolerated are eagerly sought after. For existing therapeutic strategies, there is a lack of markers that are capable of reliably predicting prognosis or the therapeutic response prior to treatment. There is hope that elucidation of the AML-specific proteome will prompt the discovery of novel therapeutic targets and biomarkers in AML. Modern mass-spectrometry instrumentation has acheived excellent performance in terms of sensitivity, resolution and mass accuracy; however, so far, the contribution of proteomics to the care of patients with AML is virtually zero. This might be partly because mass spectrometry instrumentation and protein fractionation still lack true high-throughput capabilities with highest levels of reproducibility, thus hampering large-scale translational studies with clinical samples. Since mass-spectrometry instruments are very intricate devices, their successful operation will hinge on the willingness and ability of mass-spectrometry experts and clinical researchers to adopt new views, learn from each other and cooperate in order to ultimately benefit the patient suffering from AML. This review highlights some clinical problems circumventing the treatment of patients with AML. Furthermore, it provides a brief overview of the technical background of standard proteomics approaches and describes opportunities, challenges and pitfalls of proteomic studies with regards to AML.

Keywords::

• acute myeloid leukemia
• biomarkers
• protein mass spectrometry
• protein profiling proteomics