title: Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm.
abstract: Although BCR-ABL negative myeloproliferative neoplasms (MPN)--and especially myelofibrosis (MF)--are recognized to be associated with autoimmune phenomena, immune derangements in MPN have been much less studied. Myeloid-derived suppressor cells (MDSC) are one type of important immune modulator cell. Therefore, we studied MDSCs in MPN disease. MDSCs were studied in two cohorts: the first cohort was 55 patients including 16 primary myelofibrosis (PMF), 7 post-polycythemia vera (PV)-MF, 2 post-essential thrombocythemia (ET)-MF, 11 ET, 17 PV, 2 undefined MPN disorder, and 23 normal controls; the second cohort included 38 patients: 17 ET, 7 PMF, 3 ET-MF, 2 PV-MF, 9 PV patients, and 20 normal volunteers. The second cohort was studied using freshly collected specimens and a comparable age group as controls. CD11b(+), CD14(-), and CD33(+) cells were defined as MDSCs in both cohorts by flow cytometry. Since there are no differences in MDSC levels among different MPN categories, they were grouped as MPNs. The results showed that MDSCs were significantly elevated in MPNs compared with controls in both cohorts. We also performed RT-PCR and found that MPN patients have significantly elevated arginase-1 mRNA compared with controls, and sorted MDSCs were found to have suppressor T cell activity in MPNs, substantiating the hypothesis that levels of MDSCs are, in fact, deranged in MPNs. MDSC levels were not correlated with JAK2 status, white blood cells, Hb levels, platelet counts, splenomegaly, or the degree of bone marrow fibrosis (in MF). Further studies in immune therapy involving MDSC inhibitors or differentiation may be developed to treat MPN disease.
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA. Electronic address: jcwang0005@gmail.com.
authors.forename: Jen Chin
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kundra
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
authors.forename: Mirela
authors.initials: M
authors.lastname: Andrei
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Baptiste
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
authors.forename: Ching
authors.initials: C
authors.lastname: Wong
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
authors.forename: Hemant
authors.initials: H
authors.lastname: Sindhu
mesh_terms: D000328:Adult; D000368:Aged; D001119:Arginase / Q000276:immunology / Q000378:metabolism; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053614:Janus Kinase 2 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C574619:ARG1 protein, human; D001119:Arginase
keywords: Myeloid-derived suppressor cells (MDSC); Myeloproliferative neoplasm (MPN)