Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The examination of the presence of Ph chromosome and of the fused gene BCR-ABL in patients with chronic myeloid leukemia (CML) is significant for the precise diagnosis and in some cases for the prognosis of the disease. We examined peripheral blood for the presence of BCR-ABL fused gene by polymerase chain reaction (PCR) in eight patients with CML consecutively cytogenetically studied before and after the bone marrow transplantation and in two patients treated with interferon. Southern blot analysis was performed before BMT in two patients and the molecular rearrangement of Ph chromosome was found. In all cases our results have proved that cytogenetic and recombinant DNA evaluations confirm each other. Due to the high sensitivity of PCR technique the minimal residual leukemia can be detected.
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PMID:[Use of cytogenetic and molecular biology in the detection of chronic myeloid leukemia]. 128 73

The polymerase chain reaction (PCR) cannot be used to amplify the breakpoint in the chimaeric BCR-ABL gene in CML and acute leukaemias due to the large variation in the sites of breakpoint in the BCR gene (within a 5.8 kb region) and in the ABL gene (within a 150 kb region). The disease state is usually monitored using RNA-PCR to monitor abnormal transcripts. We have used a new modification of the PCR to amplify breakpoints within zone 3 of the M-bcr. A synthetic oligonucleotide linker, the Vectorette, is ligated to restriction digested DNA, and amplification is carried out between primers for a known target sequence and the Vectorette linker. Three Philadelphia chromosome Ph1-positive CML patients with breakpoints within the ALU region of zone 3 have been amplified and the sequence immediately around the breakpoint determined. The breaks occurred within 70 bp and two were only 14 bp apart. The Vectorette-PCR technique has the potential to rapidly identify and sequence breakpoints, and will enable the design of patient-specific primers to monitor disease progression, particularly following bone marrow transplantation.
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PMID:Amplification and sequencing of genomic breakpoints located within the M-bcr region by Vectorette-mediated polymerase chain reaction. 131 90

The hallmark of chronic myelogenous leukemia is the translocation of the human c-abl protooncogene (ABL) from chromosome 9 to the specific breakpoint cluster region (bcr) of the BCR gene on chromosome 22. The t(9;22)(q34;q11) translocation results in the formation of a BCR-ABL fusion gene that encodes a 210-kDa chimeric protein with abnormal tyrosine kinase activity. The ABL and BCR genes are expressed by normal cells and thus the encoded proteins are presumably nonimmunogenic. However, the joining-region segment of the p210BCR-ABL chimeric protein is composed of unique sequences of ABL amino acids joined to BCR amino acids that are expressed only by malignant cells. The current study demonstrates that the joining region of BCR-ABL protein is immunogenic to murine T cells. Immunization of mice with synthetic peptides corresponding to the joining region elicited peptide-specific, CD4+, class II major histocompatibility complex-restricted T cells. The BCR-ABL peptide-specific T cells recognized only the combined sequence of BCR-ABL amino acids and not BCR or ABL amino acid sequences alone. Importantly, the BCR-ABL peptide-specific T cells could recognize and proliferate in response to p210BCR-ABL protein. The response of peptide-specific T cells to protein demonstrated that p210BCR-ABL can be processed by antigen-presenting cells so that the joining segment is bound to class II major histocompatibility complex molecules in a configuration similar to that of the immunizing peptide and in a concentration high enough to stimulate the antigen-specific T-cell receptor. Thus, BCR-ABL protein represents a potential tumor-specific antigen related to the transforming event and shared by many individuals with chronic myelogenous leukemia.
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PMID:T-cell immunity to the joining region of p210BCR-ABL protein. 134 32

We report a new case of Ph positive chronic myeloid leukemia (CML) without the classical rearrangement in Mbcr. By Southern blot analysis the molecular breakpoint was mapped 3 to 8 kb upstream of Mbcr. This region has not been shown to be rearranged in any other described case of CML. We did not detect any specific abnormal BCR-ABL transcript even with the use of the very sensitive RNA-PCR technique.
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PMID:A new chromosomal breakpoint in Ph positive, bcr negative chronic myelogenous leukemia. Report of a case. 135 7

The involvement of the BCRlABL fusion gene in patients with Philadelphia (Ph) chromosome positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL) is well characterised, but the molecular events underlying the cases of Ph-negative CML and ALL that lack BCR gene involvement and those that cause transformation of Ph-positive CML are unknown. The murine ABL gene can be activated by genetic events that do not involve the BCR gene, including the introduction of two specific point mutations in exons VII and XI respectively, as found in the homologous sequence of the v-abl oncogene. We therefore sought evidence for analogous point mutations in the ABL gene in patients with Ph-negative, BCR-negative CML (n = 25), Ph-negative ALL (n = 18) and in Ph-positive CML in transformation (n = 28). We used restriction fragment length polymorphism and single strand conformational polymorphism techniques to analyse DNA amplified fragments of selected ABL coding regions from leukaemia cells. We identified only normal wild-type DNA sequences. The absence of these transforming point mutations does not exclude the possibility that the ABL gene in such patients could be activated by other means.
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PMID:Specific point mutations that activate v-abl are not found in Philadelphia-negative chronic myeloid leukaemia, Philadelphia-negative acute lymphoblastic leukaemia or blast transformation of chronic myeloid leukaemia. 135 50

The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from the reciprocal translocation t(9;22) (q34;q11). On DNA level a BCR/ABL rearrangement involving the so-called major BCR (Mbcr) from chromosome 22 has been associated with chronic myeloid leukemia (CML). For Ph+ ALL a site of rearrangements in the 5' part of the BCR (breakpoint cluster region) gene on chromosome 22, the so-called minor bcr region (mbcr) has been described within the first intron in a 10.8 kb region (=bcr2 or m-BCR1). The BB1 probe detects two Eco fragments of 8.5 and/or 11 kb, which may appear as monomorphic or heteromorphic alleles, both covering bcr2. We have analyzed EcoRI restriction polymorphisms within bcr2 in 42 patients with a rearrangement in M-bcr (including 39 Philadelphia chromosome-positive (Ph+) CML patients and 3 ALLs) and in 18 healthy unrelated volunteers. Of the 42 patients tested, 52.4% (22) had the 8.5 kb bcr2 allele, 21.4% (9) had the 11 kb bcr2 allele, and 26.2% (11) had both the 8.5 and the 11 kb allele. In addition to normal allelic polymorphisms in bcr2, rRFs (rearranged bcr2 restriction fragments) were found in bcr2 as shown in 33% (14 of 42) of our patients. By contrast, no rRFs were found in 18 healthy volunteers. Our results indicate, that heterogeneous rearrangements in bcr2 may appear in addition to BCR/ABL rearrangements involving M-bcr in Ph+CML.
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PMID:Minor BCR (m-bcr) rearrangements may appear in major BCR (M-bcr)-positive CML cases. 136 28

Interferon (IFN) therapy of early chronic myelogenous leukemia (CML) frequently produces partial or complete cytogenetic remission of the disease. Patients with complete cytogenetic remission often continue on therapy for several years with bone marrow showing only diploid (normal) metaphases. We studied hematopoiesis in five female patients with major cytogenetic remissions from CML during IFN therapy. Clonality analysis using the BstXI PGK gene polymorphism showed that granulocytes were nonclonal in all patients during cytogenetic remission. BCR region studies showed rearrangement only in the one patient whose remission was incomplete at the time of sampling. Granulopoiesis is nonclonal in IFN-induced remissions of CML and may be derived from normal hematopoietic stem cells.
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PMID:Polyclonal hematopoiesis in interferon-induced cytogenetic remissions of chronic myelogenous leukemia. 137 Oct 81

We describe a patient with chronic myeloid leukemia (CML) and a 22q- but no 9q+ chromosome. Southern blot analysis showed a BCR rearrangement. The patient soon developed profound and superficial thrombophlebitis in arms and legs and died from pulmonary embolisation 15 days after diagnosis. Five CML cases with a deletion of 22q but no known translocation of 22q11----qter have been described earlier. The present patient is the first such case, however, in whom a BCR rearrangement has been demonstrated.
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PMID:Ph-positive chronic myeloid leukemia with loss of the segment distal to M-bcr. 137 17

We performed molecular studies to resolve the status of BCR and ABL in the bone marrow cells of a CML patient with a Ph chromosome resulting from a complex translocation involving chromosomes 9, 15, and 22. DNA digestion with BamHI, HindIII, and BglII, followed by hybridization to a bcr-specific 32P-labeled probe, showed a rearranged banding pattern confirming the involvement of the bcr locus in the translocation. Furthermore, total cellular RNA isolated from the marrow was subjected to reverse transcription into cDNA and amplified by PCR with primers specific for BCR-ABL fusion cDNA. The amplified products obtained from this patient and from a CML patient with the standard t(9;22) were both of the expected length of approximately 317 bp.
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PMID:Molecular confirmation of BCR-ABL fusion in a chronic myeloid leukemia with a complex translocation involving chromosomes 9, 15, and 22. 137 43

The relationship between activation of the N-RAS gene and the leukemic progression of undifferentiated chronic myeloproliferative disease (UCMPD) was investigated in a 71-year-old male. Hematologically, it was difficult to differentiate the UCMPD from chronic myelogenous leukemia. Chromosomal analysis revealed no Philadelphia chromosome (Ph1-), and DNA analysis revealed no BCR rearrangement (BCR-) either at the beginning or in the terminal stages of the disease. We performed a tumorigenicity assay, using NIH3T3 cells, and molecular analysis, using the polymerase chain reaction (PCR) and direct sequencing. The DNA of leukemic cells at the beginning of the leukemic progression did not show any abnormalities, but at the terminal stage of the disease the DNA showed a point mutation in codon 12 (GGT----GCT) of the N-RAS gene. Interestingly, a codon 13 mutation (GGT----GTT) was also detected by tumorigenicity assay. These observations suggest that the activated N-RAS gene contributes to the hematologic progression of UCMPD.
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PMID:N-RAS activation in the terminal stage of undifferentiated chronic myeloproliferative disease. 139 9


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