Proteomic Strategies for Individualizing Therapy of Acute MyeloidLeukemia (AML)

Gry Sjoholt; Siv Lise Bedringaas; Anne P. Doskeland; Bjorn Tore Gjertse

doi:10.2174/138920106777549759

Abstract

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by accumulatingmyeloid precursor cells in the bone marrow, with approximately 2-3 months 50% survival if left untreated. With currenttreatment modalities the five years overall survival hardly exceeds 50%. Cytogenetics and molecular diagnostics guide theclinician to select individualized therapy in certain subsets of AML, achieving long-term survival above 70% of thesecases. However, approximately half of the AML patients have no risk stratifying features, and early reports indicate thatproteomic approaches may be utilized for disease classification as well as development of novel biomarkers related toprognosis, diagnosis, and choice of therapeutic regimen. Proteomics, here defined as the analysis of all proteins in a cell,in a cell compartment or in a signaling pathway, has probably its greatest potential in investigating pathways that are eas-ily targeted by small molecules or therapeutic antibodies. Th e major methodological challenges include detection sensi-tivity in a limited clinical material, a problem that in some cases can be solved through designated multiplexed protein as-says based on single cells or cell extracts. In this review we will discuss pharmacoproteomic studies of drugs regulatingleukemia specific targets like all-trans retinoic acid, histone deacetylase inhibitors, proteasome inhibitors and tyrosinekinase inhibitors, as well as studies on drug resistance and graft-versus-host studies during stem cell transplantations.These studies indicate new avenues in AML diagnostics, individualized therapy design and therapy response surveillancefor the clinician.

Keywords: Biomarkers, pharmacoproteomics, all-trans retinoic acid (ATRA), tyrosine kinase inhibitors, histone deacetylaseinhibitors (HDACIs), proteasome inhibitors

« Previous Next »