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C Peschle - One of the best experts on this subject based on the ideXlab platform.

  • the Acute Promyelocytic Leukemia specific pml rarα fusion protein inhibits differentiation and promotes survival of myeloid precursor cells
    Cell, 1993
    Co-Authors: Francesco Grignani, Myriam Alcalay, Pier Francesco Ferrucci, Ugo Testa, Giampaolo Talamo, Marta Fagioli, Amedea Mencarelli, F Grignani, C Peschle
    Abstract:

    Acute Promyelocytic Leukemia is a clonal expansion of hematopoietic precursors blocked at the Promyelocytic stage. The differentiation block can be reversed by retinoic acid, which induces blast maturation both in vitro and in vivo. Acute Promyelocytic Leukemia is characterized by a 15;17 chromosome translocation with breakpoints within the retinoic acid alpha receptor (RAR alpha) gene on 17 and the PML gene, which encodes a putative transcription factor, on 15. A PML-RAR alpha fusion protein is formed as a consequence of the translocation. We expressed the PML-RAR alpha protein in U937 myeloid precursor cells and showed that they lost the capacity to differentiate under the action of different stimuli (vitamin D3 and transforming growth factor beta 1), acquired enhanced sensitivity to retinoic acid, and exhibited a higher growth rate consequent to diminished apoptotic cell death. These results provide evidence of biological activity of PML-RAR alpha and recapitulate critical features of the Promyelocytic Leukemia phenotype.

  • the Acute Promyelocytic Leukemia specific pml rarα fusion protein inhibits differentiation and promotes survival of myeloid precursor cells
    Cell, 1993
    Co-Authors: Francesco Grignani, Myriam Alcalay, Pier Francesco Ferrucci, Ugo Testa, Giampaolo Talamo, Marta Fagioli, Amedea Mencarelli, F Grignani, C Peschle
    Abstract:

    Summary Acute Promyelocytic Leukemia is a clonal expansion of hematopoietic precursors blocked at the Promyelocytic stage. The differentiation block can be reversed by retinoic acid, which induces blast maturation both in vitro and in vivo. Acute Promyelocytic Leukemia is characterized by a 15;17 chromosome translocation with breakpoints within the retinoic acid α receptor ( RARα ) gene on 17 and the PML gene, which encodes a putative transcription factor, on 15. A PML-RARα fusion protein is formed as a consequence of the translocation. We expressed the PML-RARα protein in U937 myeloid precursor cells and showed that they lost the capacity to differentiate under the action of different stimuli (vitamin D 3 and transforming growth factor β1), acquired enhanced sensitivity to retinoic acid, and exhibited a higher growth rate consequent to diminished apoptotic cell death. These results provide evidence of biological activity of PML-RARα and recapitulate critical features of the Promyelocytic Leukemia phenotype.

Stanley R. Frankel - One of the best experts on this subject based on the ideXlab platform.

  • sweet s syndrome during treatment with all trans retinoic acid in a patient with Acute Promyelocytic Leukemia
    Leukemia & Lymphoma, 1998
    Co-Authors: Banu K Arun, Stanley R. Frankel, Brenda Berberian, Norio Azumi, Harvey Luksenburg, Carl E Freter
    Abstract:

    A 46 year old male with Acute Promyelocytic Leukemia treated with all-trans retinoic acid (ATRA), developed fever, bilateral erythematous nodules in his axillary area, lower abdomen and inguinal region. Histopathologic examination of the skin biopsy revealed dense neutrophil infiltration in the dermis without vasculitis. The diagnosis of Sweet's syndrome was made. High dose methylprednisolone was administered and the lesions started to improve within 24 hours.

  • all trans retinoic acid for Acute Promyelocytic Leukemia results of the new york study
    Annals of Internal Medicine, 1994
    Co-Authors: Stanley R. Frankel, Wilson H Miller, Anna Eardley, Glenn Heller, Ellin Berman
    Abstract:

    Objective: To evaluate the safety and efficacy of all-trans retinoic acid to induce complete remission and to examine its effects on duration of remission and survival in patients with Acute Promyelocytic Leukemia. Design: Phase II evaluation and comparison with historical control patients. Setting: Tertiary care cancer referral center. Patients: Consecutive patients with morphologic diagnoses of Acute Promyelocytic Leukemia were treated during a 2-year period with all-trans retinoic acid (daily oral dose, 45 mg/m 2 ). Newly diagnosed patients discontinued the drug approximately 30 days after they achieved complete remission, at which time they received three courses of combination chemotherapy

  • the retinoic acid syndrome in Acute Promyelocytic Leukemia
    Annals of Internal Medicine, 1992
    Co-Authors: Stanley R. Frankel, Anna Eardley, Gregory Y Lauwers, Mark Weiss, Raymond P. Warrell
    Abstract:

    Abstract ▪Objective:To describe a novel complication of therapy with all-trans retinoic acid in patients with Acute Promyelocytic Leukemia. ▪Design:Case series. ▪Setting:Comprehensive cancer center...

  • differentiation therapy of Acute Promyelocytic Leukemia with tretinoin all trans retinoic acid
    The New England Journal of Medicine, 1991
    Co-Authors: Raymond P. Warrell, Stanley R. Frankel, Rohini Vyas, Agostino Tafuri, Loretta M. Itri, Wilson H Miller, Walter N. Hittelman, David A. Scheinberg, Michael Andreeff, Ann A Jakubowski
    Abstract:

    Abstract Background and Methods. Patients with Acute Promyelocytic Leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor—alpha (RAR-α). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with Acute Promyelocytic Leukemia, we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent. Results. Eleven patients with Acute Promyelocytic Leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day. Nine of the 11 patients entered complete remission. In two patients, complete remission was preceded by striking leukocytosis that then resolved despite continued drug treatment. Serial studies of cellular ...

  • differentiation therapy of Acute Promyelocytic Leukemia with tretinoin all trans retinoic acid
    The New England Journal of Medicine, 1991
    Co-Authors: Raymond P. Warrell, Stanley R. Frankel, Rohini Vyas, Agostino Tafuri, Loretta M. Itri, Wilson H Miller, Walter N. Hittelman, David A. Scheinberg, Michael Andreeff, Ann A Jakubowski
    Abstract:

    Abstract Background and Methods. Patients with Acute Promyelocytic Leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor—alpha (RAR-α). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with Acute Promyelocytic Leukemia, we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent. Results. Eleven patients with Acute Promyelocytic Leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day. Nine of the 11 patients entered complete remission. In two patients, complete remission was preceded by striking leukocytosis that then resolved despite continued drug treatment. Serial studies of cellular ...

Wilson H Miller - One of the best experts on this subject based on the ideXlab platform.

  • all trans retinoic acid for Acute Promyelocytic Leukemia results of the new york study
    Annals of Internal Medicine, 1994
    Co-Authors: Stanley R. Frankel, Wilson H Miller, Anna Eardley, Glenn Heller, Ellin Berman
    Abstract:

    Objective: To evaluate the safety and efficacy of all-trans retinoic acid to induce complete remission and to examine its effects on duration of remission and survival in patients with Acute Promyelocytic Leukemia. Design: Phase II evaluation and comparison with historical control patients. Setting: Tertiary care cancer referral center. Patients: Consecutive patients with morphologic diagnoses of Acute Promyelocytic Leukemia were treated during a 2-year period with all-trans retinoic acid (daily oral dose, 45 mg/m 2 ). Newly diagnosed patients discontinued the drug approximately 30 days after they achieved complete remission, at which time they received three courses of combination chemotherapy

  • differentiation therapy of Acute Promyelocytic Leukemia with tretinoin all trans retinoic acid
    The New England Journal of Medicine, 1991
    Co-Authors: Raymond P. Warrell, Stanley R. Frankel, Rohini Vyas, Agostino Tafuri, Loretta M. Itri, Wilson H Miller, Walter N. Hittelman, David A. Scheinberg, Michael Andreeff, Ann A Jakubowski
    Abstract:

    Abstract Background and Methods. Patients with Acute Promyelocytic Leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor—alpha (RAR-α). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with Acute Promyelocytic Leukemia, we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent. Results. Eleven patients with Acute Promyelocytic Leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day. Nine of the 11 patients entered complete remission. In two patients, complete remission was preceded by striking leukocytosis that then resolved despite continued drug treatment. Serial studies of cellular ...

  • differentiation therapy of Acute Promyelocytic Leukemia with tretinoin all trans retinoic acid
    The New England Journal of Medicine, 1991
    Co-Authors: Raymond P. Warrell, Stanley R. Frankel, Rohini Vyas, Agostino Tafuri, Loretta M. Itri, Wilson H Miller, Walter N. Hittelman, David A. Scheinberg, Michael Andreeff, Ann A Jakubowski
    Abstract:

    Abstract Background and Methods. Patients with Acute Promyelocytic Leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor—alpha (RAR-α). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with Acute Promyelocytic Leukemia, we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent. Results. Eleven patients with Acute Promyelocytic Leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day. Nine of the 11 patients entered complete remission. In two patients, complete remission was preceded by striking leukocytosis that then resolved despite continued drug treatment. Serial studies of cellular ...

Ali Bazarbachi - One of the best experts on this subject based on the ideXlab platform.

  • Acute Promyelocytic Leukemia with increased bone marrow reticulin fibrosis: Description of three cases and review of the literature
    Elsevier, 2018
    Co-Authors: Iman Abou Dalle, Samer Nassif, Ali Bazarbachi
    Abstract:

    Pathologic increase in bone marrow reticulin fibrosis can be present in many malignant hematopoietic diseases. In Acute Leukemia, one-third of patients have some degree of marrow reticulin fibrosis at presentation, which is thought to be related to cytokine release from blasts. Marrow fibrosis is particularly common in Acute megakaryoblastic Leukemia, while this change is rarely seen in Acute Promyelocytic Leukemia. Six case reports of Acute Promyelocytic Leukemia with marrow reticulin fibrosis have been described so far in the literature. Herein, we present three cases of classical Acute Promyelocytic Leukemia with increased marrow reticulin fibrosis encountered in our institution, summarizing their clinicopathologic features, treatment, and outcome to date. Awareness of the features of Acute Promyelocytic Leukemia with marrow reticulin fibrosis is important as it may guide treatment options. Keywords: Acute Promyelocytic Leukemia, Bone marrow, Case report, Fibrosis, Reticulin, Revie

  • Acute Promyelocytic Leukemia with increased bone marrow reticulin fibrosis description of three cases and review of the literature
    Hematology Oncology and Stem Cell Therapy, 2016
    Co-Authors: Iman Abou Dalle, Samer Nassif, Ali Bazarbachi
    Abstract:

    Pathologic increase in bone marrow reticulin fibrosis can be present in many malignant hematopoietic diseases. In Acute Leukemia, one-third of patients have some degree of marrow reticulin fibrosis at presentation, which is thought to be related to cytokine release from blasts. Marrow fibrosis is particularly common in Acute megakaryoblastic Leukemia, while this change is rarely seen in Acute Promyelocytic Leukemia. Six case reports of Acute Promyelocytic Leukemia with marrow reticulin fibrosis have been described so far in the literature. Herein, we present three cases of classical Acute Promyelocytic Leukemia with increased marrow reticulin fibrosis encountered in our institution, summarizing their clinicopathologic features, treatment, and outcome to date. Awareness of the features of Acute Promyelocytic Leukemia with marrow reticulin fibrosis is important as it may guide treatment options.

Francesco Lococo - One of the best experts on this subject based on the ideXlab platform.

  • current management of newly diagnosed Acute Promyelocytic Leukemia
    Annals of Oncology, 2016
    Co-Authors: Laura Cicconi, Francesco Lococo
    Abstract:

    The management of Acute Promyelocytic Leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary Leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy. The advantage of ATRA-ATO over ATRA chemotherapy has been recently demonstrated in two large randomized trials and this option has now become the new standard of care in low-risk (i.e. non-hyperleukocytic) patients. In light of its rarity, abrupt onset and high risk of early death and due to specific treatment requirements, APL remains a challenging condition that needs to be managed in highly experienced centers. We review here the results of large clinical studies conducted in newly diagnosed APL as well as the recommendations for appropriate diagnosis, prevention and management of the main complications associated with modern treatment of the disease.

  • retinoic acid and arsenic trioxide for Acute Promyelocytic Leukemia
    The New England Journal of Medicine, 2013
    Co-Authors: Francesco Lococo, Paola Fazi, Laura Cicconi, Emanuele De Bona, Simona Iacobelli, Marco Vignetti, Felicetto Ferrara, Christian Thiede, Giuseppe Avvisati, Giorgina Specchia
    Abstract:

    Background All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for Acute Promyelocytic Leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity. Methods

  • aida 0493 protocol for newly diagnosed Acute Promyelocytic Leukemia very long term results and role of maintenance
    Blood, 2011
    Co-Authors: Giuseppe Avvisati, Francesco Lococo, Marco Vignetti, Giorgina Specchia, Francesca Paoloni, M C Petti, Daniela Diverio, Roberto Latagliata, Michele Baccarani, Eros Di Bona
    Abstract:

    All- trans -retinoic acid (ATRA) has greatly modified the prognosis of Acute Promyelocytic Leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed Acute Promyelocytic Leukemia patients received ATRA plus idarubicin as induction, followed by 3 intensive consolidation courses. Thereafter, patients reverse-transcribed polymerase chain reaction–negative for the PML-RARA fusion gene were randomized into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); and no further therapy (arm 4). Starting from February 1997, randomization was limited to ATRA-containing arms only (arms 2 and 3). Complete remission was achieved in 761 of 807 (94.3%) patients, and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML-RARA fusion gene, and 586 of 646 (90.7%) who tested reverse-transcribed polymerase chain reaction–negative were randomized to maintenance. The event-free survival estimate at 12 years was 68.9% (95% confidence interval, 66.4%-71.4%), and no differences in disease-free survival at 12 years were observed among the maintenance arms.

  • modern approaches to treating Acute Promyelocytic Leukemia
    Journal of Clinical Oncology, 2011
    Co-Authors: Miguel A Sanz, Francesco Lococo
    Abstract:

    The advent of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy have contributed in the past 2 decades to optimize the antileukemic efficacy in Acute Promyelocytic Leukemia (APL), leading to complete remission rates greater than 90%, virtual absence of resistance, and cure rates of nearly 80%. Recently reported studies from large cooperative trials have also shown that more rational delivery of treatment and improved outcomes may derive from the use of risk-adapted protocols. In particular, patients at higher risk of relapse (ie, those presenting with WBC 10 10 9 /L) seem to benefit from treatments that include cytarabine in the ATRA-plus-chemotherapy scheme, whereas patients with standard-risk disease can be successfully managed with less-intensive regimens that contain ATRA and anthracycline-based chemotherapy. After the outstanding results with arsenic trioxide (ATO) in the treatment of APL relapse, several experimental trials have been designed to explore the role of ATO in front-line therapy with the aim not only of minimizing the use of chemotherapy but also to reinforce standard ATRA-plus-chemotherapy regimens and additionally improve therapeutic efficacy. In this review article, we discuss most recent advances in the treatment of patients with newly diagnosed and relapsed APL. J Clin Oncol 29:495-503. © 2011 by American Society of Clinical Oncology