Membrane proteomics for leukemia classification and drug target identification.
Knowledge of protein expression in the plasma membrane of leukemia cells has contributed to improvements in the detection and treatment of hematological malignancies. Recently engineered antibodies against leukemia surface molecules have improved therapeutic efficacy compared with earlier agents, but there are still side effects. An increased understanding of the surface expression profiles and interactions of membrane proteins on leukemia cells will facilitate the expansion of the role of antibodies in therapy and enable the identification of novel biomarkers for the various stages of leukemogenesis and leukemia progression. Proteomic analysis enables the identification of thousands of proteins in a membrane extract and provides information on their relative abundance, interactions and post-translational modifications. Plasma membrane proteome analysis of leukemia cells can be used to define biomarkers for diagnosis, classification, prognosis and progression monitoring, as well as to predict therapeutic response or resistance. The effects of chemotherapy on the surface proteome and the functional consequences of perturbations to membrane protein networks can provide insights into leukemia cell signaling and survival mechanisms. Surface proteins that are differentially expressed on leukemia cells are prospective targets for the development of engineered antibodies or small-molecule therapeutics. This review focuses on recent discoveries in leukemia membrane proteomics and the potential for future research into leukemia classification and drug target identification.
Kohnke
Philippa L
PL
University of Sydney, School of Molecular and Microbial Biosciences, Maze Crescent, Sydney, New South Wales 2006, Australia.
Mulligan
Stephen P
SP
Christopherson
Richard I
RI
D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D006801:Humans; D007938:Leukemia / Q000145:classification* / Q000188:drug therapy / Q000378:metabolism*; D008223:Lymphoma / Q000145:classification / Q000188:drug therapy / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis* / Q000302:isolation & purification; D020543:Proteome / Q000032:analysis* / Q000187:drug effects; D040901:Proteomics
D000970:Antineoplastic Agents; D015415:Biomarkers; D008565:Membrane Proteins; D020543:Proteome