Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypermetaphase FISH (HMF), a molecular cytogenetic procedure combining the long term mitotic arrest of bone marrow cultures with detection of a specific chromosomal rearrangement by fluorescence in situ hybridization (FISH), has recently been shown to be effective in determining the frequency of Philadelphia chromosome positive (Ph+) cells in the bone marrow of chronic myelogenous leukemia (CML) patients undergoing treatment. By combining the probe for the Ph chromosome with one for the detection of the X chromosome, we used HMF to monitor the presence of malignant cells within the emerging host cell population in the marrow of a CML patient that had undergone sex-mismatched allogeneic bone marrow transplantation. In successive studies, we detected 0.5% and 1.75% Ph+ cells, respectively, confirmed by Western blot analysis for p210 protein. These readings occurred concordantly with a repopulation of host-derived diploid female cells. Standard G-band cytogenetic analyses did not detect any Ph+ cells at these time points. Intervention with donor lymphocyte infusion reinduced complete remission. This experience indicates that HMF is useful to identify low levels of repopulation by Ph+ cells in the marrow post-BMT at a stage when intervention is most efficacious.
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PMID:Usefulness of detection of minimal residual disease by 'hypermetaphase' fluorescent in situ hybridization after allogeneic BMT for chronic myelogenous leukemia. 908 36

Transformed chronic myeloid leukemia (CML) has a dismal prognosis, and treatment with a variety of chemotherapeutic agents is extremely disappointing. A novel therapeutic approach was initiated to improve the outcome of this condition. Nine patients, four females and five males, with either acceleration of CML or blast crisis (myeloid), or, in two instances, both, entered this pilot study. Median age was 60 years; seven patients were Philadelphia chromosome positive; two were negative but showed a bcr/abl rearrangement. All patients had a well-defined preceding period of stable chronic phase, for which they received sequentially hydroxyurea (N = 9), interferon (IFN) (N = 3), busulfan (N = 2), melphalan (N = 1), 6-MP (N = 1), or allogeneic BMT (N = 1). Median length of preceding chronic phase to acceleration or blast crisis was 56 months. All patients responded to treatment with a starting dose of IFN (9 Mio U/day), subcutaneously, and hydroxyurea (3 g/day), orally, by reversal to chronic phase. Three of the patients responded repeatedly during their course of disease. Median time for reversal to chronic phase was 4 weeks. Adverse side effects like nausea, vomiting, hair loss, fever, and prolonged cytopenia as seen after chemotherapy were not observed. The duration of chronic phase varied, and lasted, in six instances, more than 5 months, while the Philadelphia chromosome persisted. One additional patient received an unrelated bone marrow transplantation after reaching chronic phase (+24 months). Disease progression occurred 2 months after cessation of treatment. This treatment has proven very promising so far.
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PMID:Successful treatment of accelerated and blastic phase of chronic myeloid leukemia with high-dose interferon-alpha combined with hydroxyurea. 961 49

We sought to establish a rapid and reliable RT-PCR approach for detection and quantification of BCR-ABL fusion transcripts using the LightCycler technology. This device combines rapid thermocycling with online detection of PCR product formation and is based on the fluorescence resonance energy transfer (FRET) between two adjacent hybridization probes carrying donor and acceptor fluorophores. A pair of probes was designed that was complementary to ABL exon 3, thus enabling detection of all known BCR-ABL variants and also normal ABL as an internal control. Conditions were established to amplify less than 10 target molecules/reaction and to detect one CML cell in 105 cells from healthy donors. To determine the utility of the assay, we quantified BCR-ABL and ABL transcripts in 254 samples (222 peripheral blood, 32 bone marrow) from 120 patients with CML after therapy with IFN-alpha (n = 219), allogeneic BMT (n = 17), chemotherapy (n = 11), or at diagnosis (n = 7). The level of residual disease in the 245 BCR-ABL positive specimens was expressed as the ratio of BCR-ABL/ABL. This ratio was compared to results obtained by three established methods from contemporaneous specimens. A highly significant correlation was seen between the BCR-ABL/ABL ratios determined by the LightCycler and (1) the BCR-ABL/ABL ratios obtained by nested competitive RT-PCR (n = 201, r = 0.90, P < 0. 0001); (2) the proportion of Philadelphia chromosome positive metaphases determined by cytogenetics (n = 81, P < 0.0001); and (3) the BCR ratio determined by Southern blot analysis (n = 122, P < 0. 0001). We conclude that real-time PCR with hybridization probes is a reliable and sensitive method to monitor CML patients after therapy. The major advantages of the methodology are (1) amplification and product analysis are performed in the same reaction vessel, avoiding the risk of contamination; (2) the results are standardized by the quantification of housekeeping genes; and (3) the complete PCR analysis takes less than 60 min.
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PMID:Accurate and rapid analysis of residual disease in patients with CML using specific fluorescent hybridization probes for real time quantitative RT-PCR. 1055 58

A patient with chronic phase Philadelphia chromosome positive CML, developed severe protracted bone marrow hypoplasia after interferon therapy. This complication did not respond to two courses of immunosuppressive therapy with anti-thymocyte globulin, cyclosporin A and prednisone. The patient continued to be transfusion dependent with persistence of Philadelphia chromosome. Allogeneic BMT restored normal hematopoeisis.
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PMID:Rescue of interferon induced bone marrow aplasia in a patient with chronic myeloid leukemia by allogeneic bone marrow transplant. 1506 Dec 16