title: Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors.
abstract: BACKGROUND
  Numerous subsets of patients with chronic lymphocytic leukemia display similar immunoglobulin gene usage with almost identical complementarity determining region 3 sequences. Among IGHV4-34 cases, two such subsets with "stereotyped" B-cell receptors were recently identified, i.e. subset #4 (IGHV4-34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to share biological and clinical features, e.g. young age at diagnosis and indolent disease, whereas little is known about subset #16 at a clinical level.
  
  
  METHODS
  We investigated the global gene expression pattern in sorted chronic lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using Affymetrix gene expression arrays.
  
  
  RESULTS
  Although generally few differences were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene expression profiles were revealed for subset #4 versus subset #16. The differentially expressed genes, predominantly with lower expression in subset #4 patients, are involved in important cell regulatory pathways including cell-cycle control, proliferation and immune response, which may partly explain the low-proliferative disease observed in subset #4 patients.
  
  
  CONCLUSIONS
  Our novel data demonstrate distinct gene expression profiles among patients with stereotyped IGHV4-34 B-cell receptors, providing further evidence for biological differences in the pathogenesis of these subsets and underscoring the functional relevance of subset assignment based on B-cell receptor sequence features.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Millaray
authors.initials: M
authors.lastname: Marincevic
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mansouri
authors.forename: Meena
authors.initials: M
authors.lastname: Kanduri
authors.forename: Anders
authors.initials: A
authors.lastname: Isaksson
authors.forename: Hanna
authors.initials: H
authors.lastname: Göransson
authors.forename: Karin Ekström
authors.initials: KE
authors.lastname: Smedby
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Fred
authors.initials: F
authors.lastname: Davi
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D016000:Cluster Analysis; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell
references.citation: Am J Clin Pathol. 2007 Sep;128(3):430-6
references.pmid: 17709317
references.citation: Biochem Biophys Res Commun. 2007 Apr 6;355(2):318-23
references.pmid: 17303076
references.citation: J Exp Med. 1994 Oct 1;180(4):1395-403
references.pmid: 7523571
references.citation: J Immunol. 1995 Jan 15;154(2):483-90
references.pmid: 7814861
references.citation: Blood. 2002 Mar 15;99(6):2262-4
references.pmid: 11877310
references.citation: Haematologica. 2010 Sep;95(9):1519-25
references.pmid: 20421269
references.citation: Blood. 2003 Jun 15;101(12):4952-7
references.pmid: 12586612
references.citation: Blood Cells Mol Dis. 1996;22(2):126-38
references.pmid: 8931953
references.citation: Blood. 2009 Apr 30;113(18):4309-18
references.pmid: 19196658
references.citation: Hum Antibodies. 2004;13(3):63-8
references.pmid: 15598986
references.citation: Curr Opin Genet Dev. 1994 Aug;4(4):550-5
references.pmid: 7950323
references.citation: Traffic. 2009 Aug;10(8):982-93
references.pmid: 19416474
references.citation: Blood. 1999 Sep 15;94(6):1840-7
references.pmid: 10477712
references.citation: Leukemia. 2009 Oct;23(10):1755-62
references.pmid: 19458629
references.citation: J Clin Invest. 2001 Oct;108(7):1061-70
references.pmid: 11581307
references.citation: Biostatistics. 2003 Apr;4(2):249-64
references.pmid: 12925520
references.citation: Gene Ther. 2008 Apr;15(7):473-83
references.pmid: 18273053
references.citation: J Exp Med. 2004 Aug 16;200(4):519-25
references.pmid: 15314077
references.citation: J Immunol. 2004 Apr 1;172(7):4298-307
references.pmid: 15034044
references.citation: Br J Haematol. 2009 Feb;144(4):492-506
references.pmid: 19036101
references.citation: Blood. 2009 Jan 8;113(2):403-11
references.pmid: 18948572
references.citation: Int J Oncol. 2009 May;34(5):1291-301
references.pmid: 19360341
references.citation: Autoimmunity. 2004 Feb;37(1):9-15
references.pmid: 15115306
references.citation: Blood. 2008 Jun 15;111(12):5446-56
references.pmid: 18216293
references.citation: EMBO J. 1999 Oct 15;18(20):5691-702
references.pmid: 10523312
references.citation: J Immunol. 1993 Nov 1;151(9):5011-21
references.pmid: 7691963
references.citation: Nature. 1984 Feb 9-15;307(5951):560-3
references.pmid: 6420710
references.citation: Oncogene. 2007 Apr 26;26(19):2707-16
references.pmid: 17057733
references.citation: Leukemia. 2010 Jul;24(7):1317-24
references.pmid: 20463750
references.citation: J Rheumatol. 1999 Aug;26(8):1727-33
references.pmid: 10451069
references.citation: Blood. 2004 Nov 1;104(9):2879-85
references.pmid: 15217826
references.citation: Leukemia. 2009 May;23(5):919-24
references.pmid: 19148139
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31-6
references.pmid: 11134512
references.citation: J Clin Invest. 1998 Oct 15;102(8):1515-25
references.pmid: 9788964
references.citation: Stat Appl Genet Mol Biol. 2004;3:Article3
references.pmid: 16646809
references.citation: Blood. 2005 Jul 15;106(2):681-9
references.pmid: 15817677
references.citation: Mol Cell Endocrinol. 2001 Jun 30;180(1-2):149-53
references.pmid: 11451585
references.citation: Blood. 2008 Feb 1;111(3):1524-33
references.pmid: 17959859
references.citation: J Clin Invest. 2005 Jun;115(6):1636-43
references.pmid: 15902303
references.citation: Blood. 2009 Nov 12;114(20):4460-8
references.pmid: 19713457
references.citation: Blood. 2010 May 13;115(19):3907-15
references.pmid: 20110421
references.citation: Blood. 2007 Jan 1;109(1):259-70
references.pmid: 16985177
references.citation: Blood. 1999 Sep 15;94(6):1848-54
references.pmid: 10477713