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  1. Article ; Online: Optimal timing of molecular monitoring after tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia.

    Tiribelli, Mario / Toffoletti, Eleonora / Di Giusto, Sara / Fanin, Renato / Damiani, Daniela

    European journal of haematology

    2022  Volume 110, Issue 3, Page(s) 330–331

    MeSH term(s) Humans ; Tyrosine Kinase Inhibitors ; Protein Kinase Inhibitors/adverse effects ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myeloid ; Chronic Disease
    Chemical Substances Tyrosine Kinase Inhibitors ; Protein Kinase Inhibitors
    Language English
    Publishing date 2022-12-13
    Publishing country England
    Document type Letter
    ZDB-ID 392482-8
    ISSN 1600-0609 ; 0902-4441
    ISSN (online) 1600-0609
    ISSN 0902-4441
    DOI 10.1111/ejh.13907
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    Zs.A 323: Show issues Location:
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  2. Article ; Online: JAK2 V617F-mutated polycythemia vera developing in a patient with a 20-year-long chronic myeloid leukemia at the time of first molecular response.

    Tosoni, Luca / Fabbro, Dora / Pizzano, Umberto / Mullai, Rikard / Morelli, Gianluca / Franzoni, Alessandra / Damante, Giuseppe / Toffoletti, Eleonora / Damiani, Daniela / Fanin, Renato / Tiribelli, Mario

    Annals of hematology

    2023  Volume 102, Issue 5, Page(s) 1279–1280

    MeSH term(s) Humans ; Chronic Disease ; Janus Kinase 2/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myeloid ; Mutation ; Polycythemia Vera/diagnosis ; Polycythemia Vera/genetics
    Chemical Substances JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2)
    Language English
    Publishing date 2023-03-22
    Publishing country Germany
    Document type Case Reports ; Letter
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-023-05187-5
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  3. Article ; Online: WT1 - Gene expression driven pre-emptive treatment with decitabine for molecular relapse of acute myeloid leukemia after allogeneic stem cell transplant.

    Sperotto, Alessandra / Gottardi, Michele / Candoni, Anna / Toffoletti, Eleonora / De Marchi, Roberta / Petruzzellis, Giuseppe / Pizzano, Umberto / Fanin, Renato

    Leukemia research

    2021  Volume 108, Page(s) 106587

    Language English
    Publishing date 2021-04-30
    Publishing country England
    Document type Letter
    ZDB-ID 752396-8
    ISSN 1873-5835 ; 0145-2126
    ISSN (online) 1873-5835
    ISSN 0145-2126
    DOI 10.1016/j.leukres.2021.106587
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  4. Article: A Novel ELISA-Based Peptide Biosensor Assay for Screening ABL1 Activity

    Montecchini, Oksana / Braidotti, Stefania / Franca, Raffaella / Zudeh, Giulia / Boni, Christian / Sorio, Claudio / Toffoletti, Eleonora / Rabusin, Marco / Tommasini, Alberto / Decorti, Giuliana / Stocco, Gabriele

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 749361

    Abstract: The pathogenic role of the overactivated ABL1 tyrosine kinase (TK) pathway is well recognized in some forms ... ...

    Abstract The pathogenic role of the overactivated ABL1 tyrosine kinase (TK) pathway is well recognized in some forms of
    Language English
    Publishing date 2021-11-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.749361
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  5. Article ; Online: BCR::ABL1 levels at first month after TKI discontinuation predict subsequent maintenance of treatment-free remission: A study from the "GRUPPO TRIVENETO LMC".

    Di Giusto, Sara / Toffoletti, Eleonora / Bonifacio, Massimiliano / Binotto, Gianni / Miggiano, Maria Cristina / Calistri, Elisabetta / Stulle, Manuela / Ermacora, Anna / Stella, Rossella / Scaffidi, Luigi / D'Amore, Fabio / Scotton, Giorgia / Griguolo, Davide / De Matteis, Giovanna / Bertorelle, Roberta / Krampera, Mauro / Semenzato, Gianpietro / Fanin, Renato / Damiani, Daniela /
    Tiribelli, Mario

    Cancer medicine

    2022  Volume 12, Issue 3, Page(s) 3180–3184

    Abstract: We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. ... ...

    Abstract We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087.
    MeSH term(s) Humans ; Imatinib Mesylate ; Fusion Proteins, bcr-abl/genetics ; Protein Kinase Inhibitors/pharmacology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Remission Induction
    Chemical Substances Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Protein Kinase Inhibitors
    Language English
    Publishing date 2022-10-08
    Publishing country United States
    Document type Letter
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.5158
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  6. Article: Single step multiple genotyping by MALDI-TOF mass spectrometry, for evaluation of minor histocompatibility antigens in patients submitted to allogeneic stem cell transplantation from HLA-matched related and unrelated donor.

    Cattina, Federica / Bernardi, Simona / Mantovani, Vilma / Toffoletti, Eleonora / Santoro, Alessandra / Pastore, Domenico / Martino, Bruno / Console, Giuseppe / Martinelli, Giovanni / Malagola, Michele

    Hematology reports

    2017  Volume 9, Issue 3, Page(s) 7051

    Language English
    Publishing date 2017-09-26
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2586645-X
    ISSN 2038-8330 ; 2038-8322
    ISSN (online) 2038-8330
    ISSN 2038-8322
    DOI 10.4081/hr.2017.7051
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  7. Article ; Online: Expression and modulation of S100A4 protein by human mast cells.

    Domenis, Rossana / Pilutti, David / Orsaria, Maria / Marzinotto, Stefania / Candotti, Veronica / Bosisio, Giulia / Bulfoni, Michela / Ruaro, Maria Elisabetta / Di Loreto, Carla / Mea, Vincenzo Della / Toffoletti, Eleonora / Londero, Ambrogio P / Mariuzzi, Laura / Gri, Giorgia

    Cellular immunology

    2018  Volume 332, Page(s) 85–93

    Abstract: S100A4 protein is expressed in fibroblasts during tissue remodelling and in cancer stem cells and it induces the metastatic spread of tumor cells. In mast cells (MCs) S100A4 have been found in some pathological conditions, but its function in normal MCs ... ...

    Abstract S100A4 protein is expressed in fibroblasts during tissue remodelling and in cancer stem cells and it induces the metastatic spread of tumor cells. In mast cells (MCs) S100A4 have been found in some pathological conditions, but its function in normal MCs remains to be described. The purpose of this study was to characterize the cellular localization of the S100A4 protein in MCs of human tissues with inflammatory or tumor disorders and, to determine the consequence of reducing its expression in MC response. We found that tissue resident MCs stained positive to S100A4. Both human HMC-1 cell line and resting CD34
    MeSH term(s) Antigens, CD34/metabolism ; Apoptosis/physiology ; Cells, Cultured ; Down-Regulation/physiology ; Fibroblasts/metabolism ; Humans ; Mast Cells/metabolism ; Matrix Metalloproteinase 1/metabolism ; Matrix Metalloproteinase 10/metabolism ; Neoplastic Stem Cells/metabolism ; S100 Calcium-Binding Protein A4/metabolism
    Chemical Substances Antigens, CD34 ; S100 Calcium-Binding Protein A4 ; S100A4 protein, human (142662-27-9) ; Matrix Metalloproteinase 10 (EC 3.4.24.22) ; Matrix Metalloproteinase 1 (EC 3.4.24.7)
    Language English
    Publishing date 2018-08-04
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2018.08.001
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    Zs.A 417: Show issues Location:
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  8. Article ; Online: Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia.

    Candoni, Anna / Toffoletti, Eleonora / Gallina, Roberto / Simeone, Erica / Chiozzotto, Marianna / Volpetti, Stefano / Fanin, Renato

    Clinical transplantation

    2011  Volume 25, Issue 2, Page(s) 308–316

    Abstract: WT1 is well-known to be a panleukemic marker that is expressed in 90% of acute myeloid leukemias (AML). Quantification of WT gene expression in bone marrow (BM) samples may be useful as a marker of minimal residual disease (MRD) during and after ... ...

    Abstract WT1 is well-known to be a panleukemic marker that is expressed in 90% of acute myeloid leukemias (AML). Quantification of WT gene expression in bone marrow (BM) samples may be useful as a marker of minimal residual disease (MRD) during and after treatment for early prediction of relapse. We evaluated the validity of this AML-MRD marker after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). The quantitative assessment of WT1 expression by real-time quantitative PCR (RQ-PCR) was measured in 25 patients (pts) with AML at diagnosis, at the time of RIC-SCT and after transplant at precise time points. All pts showed high WT1 levels at diagnosis with a mean of 4895 (SD 4462) and a median of 3679 (range 454-16,853) copies WT1/10(4) ABL. At transplant, 18/25 pts (72%) were in complete cytologic remission (CcR) and 7/25 (28%) had refractory AML. At the pre-SCT evaluation, BM samples from pts transplanted in CcR showed significantly lower WT1 expression levels compared to the samples from pts with refractory AML (p = 0.002). Median follow-up after RIC-SCT was 18 months (range 2-54). On 18 pts transplanted in CcR, those (17/18) who maintained CcR after RIC-SCT displayed a WT1 copy number persistently low during all the follow-up period. In patients who received RIC-SCT with active disease obtaining a sustained CcR after transplant (3/25), WT1 levels decreased to normal range in the first two months after RIC-SCT and remained low through the entire study period. All pts who relapsed after RIC-SCT (4/25) had a high WT1 copy number before the cytologic relapse. In 50% of these cases, an increase in WT1 expression was documented before molecular chimerism decreasing. With this experience, taking into account the limited number of pts, we confirmed a concordance between WT1 expression levels (measured by RQ-PCR at precise and sequential time points) and status of AML before and after RIC-SCT and we found a concordance between WT1 expression levels and hematopoietic chimerism status. Our data suggest that, in the RIC-SCT setting, the sequential and quantitative analysis of WT1 may be useful as a leukemia marker for monitoring MRD and as a predictor of overt AML cytologic relapse.
    MeSH term(s) Adult ; Aged ; Female ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/surgery ; Longitudinal Studies ; Male ; Middle Aged ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/genetics ; Neoplasm, Residual/surgery ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cell Transplantation ; Transplantation Conditioning ; Transplantation, Homologous ; WT1 Proteins/genetics ; Young Adult
    Chemical Substances RNA, Messenger ; RNA, Neoplasm ; WT1 Proteins
    Language English
    Publishing date 2011-03
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/j.1399-0012.2010.01251.x
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    Zs.A 2204: Show issues Location:
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  9. Article ; Online: High prognostic value of pre-allogeneic stem cell transplantation minimal residual disease detection by WT1 gene expression in AML transplanted in cytologic complete remission.

    Candoni, Anna / De Marchi, Federico / Zannier, Maria Elena / Lazzarotto, Davide / Filì, Carla / Dubbini, Maria Vittoria / Rabassi, Nicholas / Toffoletti, Eleonora / Lau, Bonnie W / Fanin, Renato

    Leukemia research

    2017  Volume 63, Page(s) 22–27

    Abstract: We analyzed the outcome of allogeneic stem cell transplantation (allo-SCT) in acute myeloid leukemia (AML) patients according to molecular Minimal Residual Disease (MRD) status prior to allo-SCT. MRD was assessed by the quantitative expression of the pan- ...

    Abstract We analyzed the outcome of allogeneic stem cell transplantation (allo-SCT) in acute myeloid leukemia (AML) patients according to molecular Minimal Residual Disease (MRD) status prior to allo-SCT. MRD was assessed by the quantitative expression of the pan-leukemic marker Wilms' tumor (WT1) gene, according to the validated LeukemiaNet method. Between 2005 and 2016, 122 consecutive AML patients, WT1 positive at diagnosis, received allo-SCT in cytologic complete remission (cCR). The median age at SCT was 53 years (range 18-70). Quantitative analysis of WT1 gene expression (bone marrow samples) was available in all cases both at diagnosis (100% of samples overexpressed WT1 with a mean of 8607±8187 copies/10
    Language English
    Publishing date 2017-10-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 752396-8
    ISSN 1873-5835 ; 0145-2126
    ISSN (online) 1873-5835
    ISSN 0145-2126
    DOI 10.1016/j.leukres.2017.10.010
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  10. Article ; Online: Targeting Kinase-activating Genetic Lesions to Improve Therapy of Pediatric Acute Lymphoblastic Leukemia.

    Franca, Raffaella / Kuzelicki, Natasa K / Sorio, Claudio / Toffoletti, Eleonora / Montecchini, Oksana / Poropat, Alice / Rabusin, Marco / Curci, Debora / Paladin, Dino / Stocco, Gabriele / Decorti, Giuliana

    Current medicinal chemistry

    2017  Volume 25, Issue 24, Page(s) 2811–2825

    Abstract: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 ... ...

    Abstract Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients' lymphoblasts may harbor in fact several chromosomal alterations, some of which have prognostic and therapeutic value. Of particular importance is the translocation t(9;22)(q34;q11.2) that leads to the formation of the BCR-ABL1 fusion gene, encoding a constitutively active chimeric tyrosine kinase (TK): BCR-ABL1 that is present in ~3% of pediatric ALL patients with B-immunophenotype and is associated with a poor outcome. This type of ALL is potentially treatable with specific TK inhibitors, such as imatinib. Recent studies have demonstrated the existence of a subset of BCR-ABL1 like leukemias (~10-15% of Bimmunophenotype ALL), whose blast cells have a gene expression profile similar to that of BCR-ABL1 despite the absence of t(9;22)(q34;q11.2). The precise pathogenesis of BCR-ABL1 like ALL is still to be defined, but they are mainly characterized by the activation of constitutive signal transduction pathways due to chimeric TKs different from BCR-ABL1. BCR-ABL1 like ALL patients represent a group with unfavorable outcome and are not identified by current risk criteria. In this review, we will discuss the design of targeted therapy for patients with BCR-ABL1 like ALL, which could consider TK inhibitors, and discuss innovative approaches suitable to identify the presence of patient's specific chimeric TK fusion genes, such as targeted locus amplification or proteomic biosensors.
    MeSH term(s) Child ; Fusion Proteins, bcr-abl/genetics ; Fusion Proteins, bcr-abl/metabolism ; Humans ; Janus Kinases/antagonists & inhibitors ; Janus Kinases/metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/therapeutic use ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Protein-Tyrosine Kinases/metabolism ; Pyrazoles/chemistry ; Pyrazoles/therapeutic use ; Sirolimus/chemistry ; Sirolimus/metabolism ; Sirolimus/therapeutic use ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances BCR-ABL1 fusion protein, human ; Protein Kinase Inhibitors ; Pyrazoles ; ruxolitinib (82S8X8XX8H) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Janus Kinases (EC 2.7.10.2) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2017-07-14
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 1319315-6
    ISSN 1875-533X ; 0929-8673
    ISSN (online) 1875-533X
    ISSN 0929-8673
    DOI 10.2174/0929867324666170727101932
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    Zs.A 4432: Show issues Location:
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