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  • Apoptosis  (1)
  • CLL MRD  (1)
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  • 1
    ISSN: 1279-8509
    Schlagwort(e): CLL MRD ; IgH genes rearrangement ; PCR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the absence of specific chromosomal translocations the best method for detecting minimal residual disease (MRD) in B cell malignancies is based on the uniqueness of immunoglobulin (Ig) genes rearrangement. We here report a very sensitive method for assessing MRD in complete hematological remission (CHR) chronic lymphocytic leukemia (CLL) patients as defined by the international workshop on CLL (IWCLL). Patients: Twelve CLL patients in CHR and complete phenotypic remission (CPR) were included in the study. Eight of them received Fludarabine (FDR), one was treated by Chop regimen, and the remaining 3 were rescued by polychemotherapy followed by autologous bone marrow transplantation (ABMT). Methods: DNA extracted from peripheral blood lymphocytes (PBL) of each patient was amplified with VH family specific and framework 3 primers in 5′ and a consensus JH primer in 3′, before treatment and sequentially after the CPR completion. When no clonal rearrangement could be detected by this assay, the CDR3 sequence specific probe of the clone was used as the 3′ primer, associated to the VH family specific primer in 5′. PCR products were analyzed by classical procedures in agarose and/or acrylamide gels. Results: Mixtures of leukemic cells and normal PBL showed detection of a single leukemic cell among more than 105 normal cells. Four out of the 12 patients achieved molecular remission (MR) when employing CDR3 amplifification. All 3 autografted patients were in MR, whereas only one out of the 9 patients treated by chemotherapy alone achieved MR. When using a clone specific probe, a clonal signal was observed in all cases but one (ABMT). Results presented here confirm that MR may be achieved in a few cases of B-CLL. Further studies are needed to determine the exact relationship between MRD and clinical outcome.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Hematology and cell therapy 38 (1997), S. 253-264 
    ISSN: 1279-8509
    Schlagwort(e): Apoptosis ; Blood diseases
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In this report we reviewed the recent data regarding the involvement of apoptosis or progammed cell death in hematological diseases. We summarized new features of apoptosis including high molecular weight DNA fragmentation and programmed cell death of enucleated cells. We described the recent contributions about the three oncogenes bcl-2, p53 and c-myc. New inducers and inhibitors of apoptosis have been reported, particularly the role of stromal environment, thrombopoietin, erythropoïetin and flt-3 ligand has been mentioned. Apoptosis has been studied in red cell pathology: polycythemia, thalassemia and deficiency in folates, vitamin B12, iron and G6PD. Recently, the involvement of programmed cell death has been documented in bone marrow failure and myelodysplasia. In Acute Leukemia, the therapeutic action of numerous drugs has been proven by their in vitro apoptotic effect. The resistance of malignant cells to apoptosis, in Chronic Myeloid Leukemia, due to bcr-abl oncogene, has been partially explained by conformational changes in p53 expression and is reversed by retinoic acid. Numerous reports in Chronic Lymphocytic Leukemia have documented the major role of apoptosis in this disease, especially in therapeutic efficacy of Chlorambucil, Fludarabine and Methylxanthine derivatives. At least, in Myeloma, it has been shown that apoptosis is induced by dexamethasone and HMBA, and inhibited by interleukine 6 that prevents activation of SAP Kinases.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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