title: The function of a novel immunophenotype candidate molecule PD-1 in chronic lymphocytic leukemia.
abstract: Programmed death-1 (PD-1) is a negative receptor expressed on lymphocytes including malignant B cells in chronic lymphocytic leukemia (CLL). In this work, we found that patients with CLL had a higher expression of PD-1 transcript (PDCD1) than healthy volunteers (p < 0.0001). PDCD1 expression was comparable between CLL cells from accumulation (peripheral blood) and proliferation (bone marrow) disease compartments. In blood samples of patients with mutated IGHV genes PDCD1 expression was higher than with unmutated IGHV (p = 0.0299). We demonstrated that phosphorylation of SYK and LYN, key B-cell receptor signaling kinases, was independent of PD-1 expression in patients with CLL, while ZAP-70 phosphorylation in negative tyrosine residue 292 showed strong inverse correlation (r = - 0.8, p = 0.0019). No associations between five single nucleotide polymorphisms of PDCD1, their expressions and susceptibility to CLL were found. In conclusion, PD-1 might be an independent, universal marker of CLL cells and a part of their activated phenotype, and subsequently might modulate the function of ZAP-70.
authors: a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.
authors: Maciej
authors: M
authors: Grzywnowicz
authors: b Department of Experimental Therapy , Institute of Immunology and Experimental Therapy, Polish Academy of Science , Wroclaw , Poland.
authors: Lidia
authors: L
authors: Karabon
authors: a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.
authors: Agnieszka
authors: A
authors: Karczmarczyk
authors: a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.
authors: Malgorzata
authors: M
authors: Zajac
authors: a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.
authors: Katarzyna
authors: K
authors: Skorka
authors: a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.
authors: Joanna
authors: J
authors: Zaleska
authors: a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.
authors: Paulina
authors: P
authors: Wlasiuk
authors: c Department of Hematooncology and BMT Unit , Medical University of Lublin , Lublin , Poland.
authors: Sylwia
authors: S
authors: Chocholska
authors: c Department of Hematooncology and BMT Unit , Medical University of Lublin , Lublin , Poland.
authors: Waldemar
authors: W
authors: Tomczak
authors: d Department of Clinical Immunology , Medical University of Lublin , Lublin , Poland.
authors: Agnieszka
authors: A
authors: Bojarska-Junak
authors: c Department of Hematooncology and BMT Unit , Medical University of Lublin , Lublin , Poland.
authors: Anna
authors: A
authors: Dmoszynska
authors: b Department of Experimental Therapy , Institute of Immunology and Experimental Therapy, Polish Academy of Science , Wroclaw , Poland.
authors: Irena
authors: I
authors: Frydecka
authors: a Department of Experimental Hematooncology , Medical University of Lublin , Lublin , Poland.|c Department of Hematooncology and BMT Unit , Medical University of Lublin , Lublin , Poland.
authors: Krzysztof
authors: K
authors: Giannopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D061026:Programmed Cell Death 1 Receptor; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases
keywords: BCR signaling; Chronic lymphocytic leukemia (CLL); PD-1 (CD279); PDCD1 polymorphism