title: Circulating classical CD14++CD16- monocytes predict shorter time to initial treatment in chronic lymphocytic leukemia patients: Differential effects of immune chemotherapy on monocyte-related membrane and soluble forms of CD163.
abstract: Three main monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++, differentially regulate tumor growth and survival. Thereby, in the present study we aimed to determine the role of distinct monocyte subsets in the prognostication of chronic lymphocytic leukemia (CLL). Moreover, we set out to analyze the effects of standard immune chemotherapy on different monocyte subsets and levels of membrane-associated and soluble forms of CD163, a monocyte/macrophage-related immunomodulatory protein. We demonstrated that the number of peripheral blood classical CD14++CD16- monocytes assessed at the time of diagnosis was negatively correlated with lymphocytosis and was decreased in the CLL patients who required immediate treatment as opposed to patients who qualified to 'watch and wait' strategy. Notably, lower baseline levels of classical CD14++CD16- monocytes in CLL patients who were qualified for 'watch and wait' therapy were associated with shorter time to initial treatment. Notably, therapy with rituximab, cyclophosphamide and fludarabine resulted in a significant reduction in the number of non-classical CD14+CD16++ monocytes and soluble form of CD163 but upregulation of membrane-associated monocyte CD163. Our data indicate that distinct monocyte subsets and two forms of CD163 are differentially modulated by both CLL and immune chemotherapy. Moreover, we proposed that quantification of classical monocytes at the time of diagnosis contributes to better prognostication of CLL patients.
authors.affiliation: Department of Hematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Lapuc
authors.affiliation: Department of Hematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Bolkun
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Eljaszewicz
authors.affiliation: Department of Hematological Diagnostics, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rusak
authors.affiliation: Department of Hematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Luksza
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Paula
authors.initials: P
authors.lastname: Miklasz
authors.affiliation: Department of Hematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Piszcz
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Ptaszynska-Kopczynska
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jasiewicz
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Kaminski
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Milena
authors.initials: M
authors.lastname: Dabrowska
authors.affiliation: Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bodzenta-Lukaszyk
authors.affiliation: Department of Hematology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000276:immunology; D002452:Cell Count; D019070:Cell Lineage / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000097:blood / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000097:blood* / Q000276:immunology; D017452:Receptors, IgG / Q000097:blood* / Q000276:immunology; D000069283:Rituximab / Q000008:administration & dosage; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine