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Titolo:
NEW INSIGHTS IN BIOLOGY AND CURRENT THERAPEUTIC OPTIONS FOR PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA
Autore:
CARELLA AM; FRASSONI F; MELO J; SAWYERS C; EAVES C; EAVES A; APPERLEY J; TURA S; HEHLMANN R; REIFFERS J; LERMA E; GOLDMAN J;
Indirizzi:
AZIENDA OSPED & CLIN UNIV CONVENZIONATE,OSPED SAN MARTINO GENOVA,HEMATOL & ABMT UNIT I-16132 GENOA ITALY ROYAL POSTGRAD MED SCH,DEPT HEMATOL LONDON ENGLAND UNIV CALIF LOS ANGELES,SCH MED,DIV HEMATOL ONCOL LOS ANGELES CA 90024 BRITISH COLUMBIA CANC AGCY,TERRY FOX LAB,DIV HEMATOL VANCOUVER BC V5Z1L3 CANADA IST EMATOL L & A SERAGNOLI BOLOGNA ITALY UNIV HEIDELBERG,KLINIKUM MANNHEIM,MED KLIN 3 D-6900 HEIDELBERG GERMANY CHU BORDEAUX,HOP HAUT LEVEQUE,SERV HEMATOL BORDEAUX FRANCE
Titolo Testata:
Haematologica
fascicolo: 4, volume: 82, anno: 1997,
pagine: 478 - 495
SICI:
0390-6078(1997)82:4<478:NIIBAC>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC MYELOID-LEUKEMIA; CHRONIC GRANULOCYTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; P210 BCR-ABL; CHRONIC MYELOCYTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; HYBRID MESSENGER-RNA; PHILADELPHIA-CHROMOSOME; INTERFERON-ALPHA; TYROSINE PHOSPHORYLATION;
Keywords:
CHRONIC MYELOGENOUS LEUKEMIA; ONCOGENES; STEM CELLS; TRANSPLANTATION; INTERFERON; CHEMOTHERAPY;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
173
Recensione:
Indirizzi per estratti:
Citazione:
A.M. Carella et al., "NEW INSIGHTS IN BIOLOGY AND CURRENT THERAPEUTIC OPTIONS FOR PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA", Haematologica, 82(4), 1997, pp. 478-495

Abstract

Background and Objective. From the discovery of the Ph-chromosome, there has been an extraordinary progress in our understanding of chronicmyeloid leukemia (CML). During the last three decades, new findings arising from dissection of the genetic abnormalities at a molecular level have received the most attention, but there have also been important new observations arising from studies of the biologic behaviour of normal and leukemic stem cells and, more recently, from clinical investigations. In this review we first report: the most important observations relevant to understanding the oncogenic potential of the BCR-ABL chimeric gene, and the behaviour and the relationships of normal and leukemic stem cells. From a clinical point of view, allogeneic stem celltransplantation is the only procedure able to cure CML. The main issues are: who can receive this procedure, and when and how it can be given. The situation is more complex in unrelated transplants. In patients without HLA compatible donors, many large trials in different countries have demonstrated that interferon alpha therapy is indicated and effective in the majority of patients. On the other hand, autologous stem cell transplantation is still an experimental procedure. These aspects will be analyzed in detail and, at the end, a therapeutic algorithm of a possible approach to the patients with untreated CML is provided. Evidence and Information Sources. The method used for preparing this review was an informal consensus development. All the authors of thepresent review have been working in the field of chronic myeloid luekemia, and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index(R) and Medline(R). State of Art and Perspectives. The oncogenic potential of BCR-ABL has been demonstrated in a number of in vitro and in vivo model systems. Current research efforts are focused on defining the mechanism by which BCR-ABL transforms primary hematopoietic cells. The fact that BCR-ABL contains tyrosine residues, an SH2 domain, an SH3 domain, and proline-rich sequences raises the possibility of multiple protein-protein interactions. Indeed, BCR-ABL is reported to bind and/or phosphorylate more than 20 proteins. The insights into thesignal transduction pathways activated by BCR-ABL will hopefully provide a new basis for the treatment of CML patients. Clinical evidence of the existence of a transplantable CML stem cell population has recently been extended to xenogeneic recipients of transplanted CML cells and by retroviral marking to autograft recipients, The potential of using immunodeficient mice as recipients of CML stem cells to create an in vive model of chronic phase CML should be invaluable For testing novel therapies designed to eliminate residual disease in the patient. Current therapeutic options include conventional chemotherapy, IFN-a andallogeneic stem cell transplantation as established procedures, and autografting as an experimental procedure,While IFN-a as a first line therapy does not seem to jeopardize further treatments, autografting, according to the Genoa approach or other procedures, i.e. Ph-positive cells collected at diagnosis without mobilization therapy, raises the question of an ideal sequential strategy in the management of CML patients. There seems to be a general agreement that a patient less than 50years old, with an HLA identical sibling, should receive an allogeneic stem cell transplant. This approach should be offered also to younger patients (less than or equal to 40 years) who are able to find an unrelated matched donor. Since it seems that the normal hematopoietic reservoir declines with time, it may be desiderable to mobilize and collect peripheral stem cells in order to store Ph-negative progenitors assoon after diagnosis as possible when the WBC count has been controlled by hydroxyurea while searching For a MUD is proceeding. Then six-eight months should be allowed for a MUD search. If the donor is not found, the patient may undergo autografting with the previously stored Ph-negative progenitors followed by IFN-a therapy. However, at this moment, this is an experimental procedure and must be employed only in selected centers. (C) 1997, Ferrata Storti Foundation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 02:25:36