title: Azacitidine improves the T-cell repertoire in patients with myelodysplastic syndromes and acute myeloid leukemia with multilineage dysplasia.
abstract: Patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) with multilineage dysplasia show several immunological abnormalities. In this clinical setting, by combining flow cytometry and CDR3 spectratyping we monitored the kinetic of the T-cell repertoire during Azacitidine treatment, in order to explore its potential ability to reverse the immune derangement typical of these disorders. We firstly demonstrated by flow cytometry an increase in both CD4+ and CD8+ T-cell frequencies after starting treatment. Moreover, when monitored by spectratyping our patients showed significant changes in their T-cell receptor (TCR) CDR3 profiles, which were much more evident in helper T-cells. In fact, the frequency of BV (beta variable) subfamilies showing a skewed CDR3 profile significantly decreased from baseline to the following evaluations in CD4+ T-cells (81% vs. 70%). This pattern was even more pronounced in patients responding to Azacitidine (90% vs. 61%). Our data show that the overall derangement of the T-cell repertoire detectable in patients with MDS and AML with multilineage dysplasia gradually improves during Azacitidine treatment. These findings therefore suggest that Azacitidine could be potentially able, not only to restore the hematopoietic function, but also to reverse the immune derangement typical of these hematologic disorders.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy. Electronic address: cfozza@uniss.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fozza
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Corda
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Barraqueddu
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Virdis
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Contini
authors.affiliation: Department of Haematology, King's College Hospital, London, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galleu
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Isoni
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Dore
authors.affiliation: UO Ematologia e CTMO Ospedale Oncologico A. Businco, Cagliari, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Angelucci
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Longinotti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D019070:Cell Lineage / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011948:Receptors, Antigen, T-Cell; D001374:Azacitidine
keywords: Acute myeloid leukemia with multilineage dysplasia; Azacitidine; Flow cytometry; Myelodysplastic syndromes; Spectratyping; T-cell receptor (TCR) repertoire