title: High expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 and 8 in primary myelofibrosis.
abstract: Primary myelofibrosis (PMF) is characterized by leukoerythroblastic anemia with circulating immature myeloid cells, including CD34+ cells, progressive splenomegaly and accumulation of connective tissue and neoangiogenesis in the bone marrow. Altered bone marrow stroma and cell adherence account for the egress of CD34+ cells from the bone marrow. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 has been implicated in cell adhesion, cellular invasiveness, angiogenesis, and inflammation, which are all key processes in the pathophysiology of PMF. Accordingly, CEACAMs may play an important role in these processes in patients with myelofibrosis as well. Using a genome-wide approach, several genes of the CEACAM family were found to be deregulated in patients with PMF and related myeloproliferative neoplasms (n=69). In PMF patients, the CEACAM6 and 8 were significantly upregulated (fold change (FC) 12.5 and 14.0, respectively and FDR adjusted p values 7.71×10(-7) and 1.48×10(-5), respectively). The elevated expression of CEACAM genes may reflect clonal myeloid expansion and neutrophil activation being most exaggerated in patients with PMF. Alternatively, the highly elevated gene expression of CEACAM6 and 8 in PMF may be molecular markers of myelofibrotic transformation, implying enhanced proteolytic activity, egress of CD34+ cells into the circulation, and neoangiogenesis.
authors.affiliation: Department of Hematology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark. hans.hasselbalch@dadlnet.dk
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
authors.forename: Vibe
authors.initials: V
authors.lastname: Skov
authors.forename: Thomas Stauffer
authors.initials: TS
authors.lastname: Larsen
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.forename: Caroline Hasselbalch
authors.initials: CH
authors.lastname: Riley
authors.forename: Morten K
authors.initials: MK
authors.lastname: Jensen
authors.forename: Ole Weis
authors.initials: OW
authors.lastname: Bjerrum
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D018952:Antigens, CD34 / Q000032:analysis / Q000096:biosynthesis; D015415:Biomarkers / Q000097:blood*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000235:genetics; D018375:Neutrophil Activation / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D055728:Primary Myelofibrosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; C504117:CEACAM6 protein, human; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins