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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 338 (1994), S. 175-178 
    ISSN: 0014-5793
    Keywords: BCR/ABL ; Chronic myelogenous leukemia ; Ribozyme
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Chronic myelogenous leukemia ; Allogeneic bone marrow transplantation ; Minimal residual disease ; BCR/ABL mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosomepositive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 104–5 to one cell in 105–6. Eight of 16 patients were negative by two-step PCR 1–39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Key words bcl-2 ; Ribozymes ; Programmed cell death ; Chronic myelogenous leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used synthetic RNA transcripts to prove the cleavage capability of ribozymes targeted against bcl-2-related RNAs. No cleavage occurred when control oligonucliotides were used. To assess the functional role of the specific ribozymes in chronic myelogenous leukemia (CML) cell lines we cultured K562, BV173, and Daudi cells for 48 h after lipofection with 10 μM oligonucleotide. An increase in apoptotic cells, dependent on ribozyme specificity, was shown in BV173 cells.This finding was underlined by the typical morphological changes, but there is no correlation with regard to the level of bcl-2 protein expressed. Though bcl-2 appears to interfere with cell death in myeloid cells, bcl-2-targeted ribozymes do not induce programmed cell death (PCD) by reducing bcl-2 protein levels, but rather by a presently unknown mechanism.
    Type of Medium: Electronic Resource
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