title: Use of a high sensitive nanofluidic array for the detection of rare copies of BCR-ABL1 transcript in patients with Philadelphia-positive acute lymphoblastic leukemia in complete response.
abstract: Monitoring of minimal residual disease (MRD) by quantification of BCR-ABL1 transcript levels has become a main part of the management of patients with BCR-ABL1-positive acute lymphoblastic leukemia (ALL) in treatment with tyrosine kinase inhibitors (TKIs). The failure to achieve molecular negativity shortly after starting TKI has been demonstrated to be predictive of relapse, suggesting that an accurate measurement of low BCR-ABL1 levels may have a role in preventing hematological relapse. Despite the big efforts made by many European laboratories within the European Study Group, at the time of writing a standardized procedure to quantify and express results is still missing for BCR-ABL1-positive ALL. In this study, in order to detect with high sensitivity low levels of BCR-ABL1 transcripts, we used a new technology and a new molecular approach based on microfluidic digital polymerase chain reaction (dPCR) using Taqman chemistry and we compared obtained results with those generated by the conventional method based on reverse transcriptase PCR reaction (RQ-PCR) for BCR-ABL1 and total ABL1, with TaqMan chemistry and with Applied Biosystems instrument. We demonstrated the dPCR is high-sensitive (able to detect a single copy of BCR-ABL1) and reliable (results are comparable to those obtained by BCR-ABL1 quantification with conventional technology), allowing an accurate monitoring of BCR-ABL1-positive ALL patients in complete remission.
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lonetti
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Venturi
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Papayannidis
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ottaviani
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Abbenante
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolini
authors.affiliation: Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bresciani
authors.affiliation: Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Potenza
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Parisi
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Hematology, University of Brescia, Brescia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cattina
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.affiliation: Hematology, University of Brescia, Brescia, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.affiliation: Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Luppi
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy. Electronic address: giovanni.martinelli2@unibo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D036103:Nanotechnology; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis*; D014158:Transcription, Genetic
chemical_list: C581634:BCR-ABL1 fusion protein, human; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1; Leukemia; Minimal residual disease