Serum Proteomics in the Diagnosis and Treatment of Haematological Malignancies

Sandra      Smieszek; Julian      Bailes; Mikhail      Soloviev

doi:10.2174/157016410792928161

Abstract

Application of serum proteomics and peptidomics to the field of haematological malignancies can lead to an in depth understanding of the evolution of leukemogenesis, offering potential for early diagnosis, individualized and molecularly specific treatments, and disease surveillance through the monitoring of protein signatures. Currently, the limited understanding of aetiology prevents curative treatments for haematological malignancies. Until recently, the primary focus was on cytogenetics. Gene expression profiling and metaphase karyotyping has been done extensively, yet the lack of correlation between transcript and protein has limited the comprehensiveness of these approaches. Transcriptomics has dominated the field with significant emphasis being placed upon SNP genotyping, copy number variation analysis, DNA sequencing and methylation profiling. However, the integration of the existing knowledge with proteomics is needed to discover the molecular mechanisms of haematological malignancies and for the development of diagnostic tests. Proteomic analysis allows for direct assessment of the expressed, modified and degraded proteins. The Human Serum and Plasma Proteome Projects coupled with advancing technologies with increased sensitivity and throughput are beginning to produce productive breakthroughs including new markers for the detection of early stages of leukaemias and lymphomas. This review summarizes recent research efforts in the field of haematological malignancies, and examines relevant high throughput proteomic technologies, limitations, and pathophysiological background. A broader perspective on candidates for marker panels for the detection of malignant transformations is discussed.

Keywords: Mass spectrometry, human serum proteome, protein profiling, haematological markers, posttranslational modifications, high throughput, clinical diagnosis, genotype-phenotype gap, Serum Proteomics, Haematological Malignancies, Leukemogenesis, Genotype phenotype gap, Breast cancers, Haematological diseases, High sensitivity, High resolution techniques, Multiple Myeloma, Acute Lymphoblastic Leukaemia (ALL), Chronic Myelogenous Leukaemia (CML), Hodgkin's disease, Non-Hodgkin lymphoma, Ring Sideroblasts (RARS), Refractory Anaemia (RA), Refractory Anaemia with Excess Blasts (RAEB), Post Translational Modifications (PTMs), Serum, Plasma protein analyses, Immunoglobulins, Haptoglobin, α1-anti-trypsin, Transferrin constitute, Alpha-fetoprotein, Human proteome organization (HUPO), Signalling, Necrosis, Apoptosis, Haemolysis, Neutrophil granulocytes, Mini-peptidome, Linear discriminant analysis, α1-acid glycoprotein (AGP), Capillary electrophoresis-mass spectrometry (CE-MS), Capillary electrophoresis (CE), Cancer immunomics, Post-translational modification, Natural killer cell lymphoma, Haematological disorders, Leukocyte proteomics