title: An increased expression of PI-PLCβ1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes.
abstract: This study tested the hypothesis that PI-PLCβ1 is associated with myeloid differentiation and that its expression could be useful for predicting the response of MDS patients to azacitidine, as the clinical effect of epigenetic treatments is often detectable only after several cycles of therapy. To this end, PI-PLCβ1 was quantified on 70 MDS patients (IPSS risk: 13 Low, 20 Int-1, 31 Int-2, 6 High) at baseline and during the first 3 cycles of azacitidine. Results were then compared with the hematologic response, as assessed after the sixth cycle of azacitidine therapy. Overall, 60 patients completed 6 cycles of azacitidine, and for them, a clinical and molecular evaluation was possible: 37 of these patients (62%) showed a specific increase of PI-PLCβ1 mRNA within the first 3 cycles, which was associated with a longer duration of response and with an increased myeloid differentiation, as evidenced by PI-PLCγ2 induction and the recruitment of specific myeloid-associated transcription factors to the PI-PLCβ1 promoter during azacitidine response. Moreover, the increase of cyclin D3 gene expression throughout all of the therapy showed that PI-PLCβ1-dependent signaling is indeed activated in azacitidine responder patients. Taken together, our results show that PI-PLCβ1 quantification in MDS predicts the response to azacitidine and is associated with an increased myeloid differentiation.
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Finelli
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mongiorgi
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Clissa
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Costanza
authors.initials: C
authors.lastname: Bosi
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Quaranta
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Parisi
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Stanzani
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ramazzotti
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Giulia A
authors.initials: GA
authors.lastname: Mariani
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Billi
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Manzoli
authors.affiliation: *Cellular Signalling Laboratory, Institute of Human Anatomy, Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy; Institute of Hematology "L. e A. Seràgnoli," S. Orsola-Malpighi University Hospital, Bologna, Italy; Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy; Unit of Blood Disease and Stem Cell Transplantation, University of Brescia, Italy; and Hematology Unit, Ospedale Civile di Piacenza, Italy matilde.follo@unibo.it.
authors.forename: Matilde Y
authors.initials: MY
authors.lastname: Follo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000201:enzymology; D022423:Myeloid Cells / Q000201:enzymology; D054799:Phospholipase C beta / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C518033:PLCB1 protein, human; D054799:Phospholipase C beta; D001374:Azacitidine
keywords: epigenetic therapy; gene expression; hematological malignancies; methylation; phospholipase C β1