Review Proteomic analysis of B-cell malignancies Robert S. Boyd, Martin J.S. Dyer, Kelvin Cain ⁎ MRC Toxicology Unit, Hodgkin Building, Lancaster Rd, University of Leicester, Leicester, LE1 9HN, UK ARTICLE INFO ABSTRACT The identification of proteins aberrantly expressed in malignant B-cells can potentially be used to develop new diagnostic, prognostic or therapeutic targets. Proteomic studies of B-cell malignancies have made significant progress, but further studies are needed to increase our coverage of the B-cell malignant proteome. To achieve this goal we stress the advantages of using sub-cellular fractionation, protein separation, quantitation and affinity purification techniques to identify hitherto unidentified signalling and regulatory proteins. For example, proteomic analysis of B-cell plasma membranes isolated from patients with mantle cell lymphoma (MCL) identified the voltage-gated proton channel (HVCN1,[1]). This protein has now been characterised as a key modulator of B-cell receptor (BCR) signalling and abrogation of HVCN1 function could have a role in the treatment of B-cell malignancies dependent on Keywords: Proteomics B-cell lymphomas Plasma membrane JOURNAL OF PROTEOMICS 73 (2010) 1804 – 1822 Abbreviations: mRNA, messenger RNA; BCL2, B-cell, CLL/lymphoma 2; BCL6, B-cell CLL/lymphoma 6; NF-κB, nuclear factor of kappa light chain gene enhancer in B-cells; IRF4, interferon regulatory factor 4; MALT, mucosa associated lymphoid tissue; RB1, retinoblastoma1; DLBCL, diffuse large B-cell neoplasms; FDC, follicular dendritic cell; T–NK neoplasms, T cell and NK-cell neoplasms; sIg, surface immunoglobulin; IGV, immunoglobulin variable region; Cy, fluorescent cyanide; MCL, mantle cell lymphoma; STMN1, stathmin 1; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; AZC, 5-azacytidine; CD, cellular differentiation antigen; TNFSF, member 12 tumour necrosis factor superfamily member 12; GRAVY, grand average of hydropathy; MudPIT, multi-dimensional LC–MS/MS; SILAC, stable isotope labelling of amino acids in culture; iTRAQ, isobaric tagging for relative and absolute quantification; cICAT, cleavable form of ICAT; CLL, chronic lymphocytic leukemia; SLL, small lymphocytic leukemia; M-CLL, mutated chronic lymphocytic leukemia; UM-CLL, unmutated chronic lymphocytic leukemia; COX G, carbon monoxide dehydrogenase subunit G; PTKs, protein tyrosine kinases; BCR/ABL, fusion transcript consisting of BCR and ABL; PAI, protein abundance index; SAF, spectral abundance factor; NSAF, normalised spectral abundance factor; APEX, absolute protein expression; SRM, selective reaction monitoring; 5-LO, 5-lipoxygenase; Cbp, Csk-binding protein; PPMS, purified plasma preparations; HLA, human leukocyte antigen; BCR, B-cell antigen receptor complex; lo, ordered lipid; ld, disordered lipid; ITAMS, immunoreceptor tyrosine-based activation motifs; DRM, detergent resistant membrane; Lyn, V-yes-1 Yamaguchi sarcoma viral related oncogene homolog; Btk, bruton tyrosine kinase; Vav, proto-oncogene vav; SHIP, SH2 domain-containing inositol phosphatase; siRNA, short, interfering RNAs; Raftlin, raft linking protein; CSK, C-SRC tyrosine kinase; SYK, spleen tyrosine kinase; GITR, glucocorticoid independent TNFR-related gene product; Sulfo-NHS biotin sulfosuccinimidyl biotin, sulfo-NHS-SS-biotin sulfosuccinimidyl-2-(biotinamido)-ethyl-1,3′-dithiopropionate; PGNaseF, N-glycosidase F; CSC, cell surface capturing; BAFF-R, B-cell activation factor of the TNF family; APRIL, apoptosis proliferation inducing ligand; TAC1, cyclophilin ligand interactor; BMCA, B-cell maturation antigen; NHL, non-Hodgkin lymphoma; PI3K, phosphoinositide-3 kinase; AKT, AKT kinase; PIM2, PIM2 kinase; EIF4E, eukaryotic initiation factor 4E; MYC, v-myc myelocytomatosis viral oncogene; MCL1, myeloid leukemia cell differentiation protein; TRAIL, TNF-related apoptosis-inducing ligand; HDAC, histone deacetylases, DISC, death inducing signalling complex; FADD, Fas-associated protein with Death Domain; c-FLIP, FADD-like apoptosis regulator; RIP, receptor interacting protein; TRAF2, TNF receptor associated factor 2; PRMT5, protein arginine methyltransferase 5; His, polyhistidine tag; DR4, death receptor 4; DR5, death receptor 5; CXCR4, CXC motif receptor 4; HVCN1, hydrogen voltage-gated channel 1; Fas, Apoptosis stimulating fragment receptor; FDA, Food and Drug Administration; CML, chronic myelogenous leukemia; TEL-ARG, a fusion transcript consisting of TEL and the kinase domain of ARG; JAK, Janus kinase STAT5 signal transducers and activators of transcription 5; TAP, tandem affinity purification; SNP, single nucleotide polymorphism; EGFR, epidermal growth factor receptor. ⁎ Corresponding author. Tel.: +44 116 252547; fax +44 116 2525616. E-mail address: kc5@le.ac.uk (K. Cain). 1874-3919/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jprot.2010.03.010 available at www.sciencedirect.com www.elsevier.com/locate/jprot