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)

High dose hydroxyurea (HU) was used in a pilot study to assess its efficacy in mobilizing Philadelphia (Ph) chromosome negative progenitor cells in chronic myeloid leukaemia (CML). Five patients received 12 g/M2 oral HU in divided doses. Side effects were minimal, allowing outpatient administration. Nine to fourteen days later 4 patients achieved a mean leukocyte nadir of 3.5 x 10(9)/L (Range 2.4-4.9) and a mean platelet nadir of 99 x 10(9)/L (Range 95-108). Peripheral blood mononuclear cells (PB-MNC) sampled prior to the HU priming were 100% Ph positive. Between 10 and 18 days post HU, 3 patients achieved a marked reduction (80-100%) in the number of Ph positive metaphases in PB-MNC collected by apheresis. One patient failed to achieve any Ph suppression. Polymerase chain reaction analysis (PCR) for the bcr-abl fusion product remained positive in all samples. Rapid rises in CFU-GM numbers were associated with a return to 100% Ph positive metaphases however slower rises represented recovery with predominantly Ph negative cells, allowing apheresis collection of these cells. We conclude that HU induces a reproducible leukocyte nadir with sufficient stem cell mobilization for potential autologous transplantation. Higher doses of HU together with early and intensive apheresis is required to maximize Ph negative progenitor cell harvests.
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PMID:High dose hydroxyurea in collection of Philadelphia chromosome-negative stem cells in chronic myeloid leukaemia. 837 26

Polymerase chain reaction amplification of reverse transcription products has demonstrated the presence of abl-bcr hybrid mRNAs in RNA from peripheral blood leucocytes of Philadelphia-chromosome-positive chronic myeloid leukaemia patients; such hybrid mRNAs can contain either of the alternative first exons of c-abl. A survey of 12 CMLs has shown that abl-bcr mRNAs occur in the leucocytes of some, but not all, patients, and that they are present both in chronic-phase and acute-phase leucocytes.
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PMID:ABL-BCR mRNAs transcribed from chromosome 9q+ in Philadelphia-chromosome-positive chronic myeloid leukaemia. 848 22

A patient in a blastic phase of chronic myelocytic leukemia developed multiple arterial emboli that originated from mitral valve vegetation. The diagnosis of infective endocarditis was not confirmed because blood cultures, serological assays and other examinations detected no pathogens. He died of intracranial hemorrhage after thrombolytic manipulation for embolization of the abdominal aorta and an autopsy was performed. Polymerase chain reaction analysis and Southern blot analysis of tissues from the mitral valve revealed Aspergillus species as the cause of the endocarditis, although none of the tissue specimens were culture-positive. These molecular analyses will be useful in the diagnosis of various types of Aspergillus infections.
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PMID:Aspergillus endocarditis in a leukemia patient diagnosed by a PCR assay. 912 14

K562 is a cell line with two acrocentric marker chromosomes containing abnormally banded regions (ABRs), derived from a Ph-positive chronic myelogenous leukemia (CML) patient. Using reverse and forward chromosome painting FISH analysis, we found that 9q34, 13q31, and 22q11 regions co-amplified in the ABRs-bearing acrocentric marker chromosomes of K562. Utilizing the ABRs of the cell line as target DNA for cDNA selection, we established a simple procedure for chromosome region-specific cDNA isolation. After first strand cDNA synthesis from fetal brain mRNAs, short fragment cDNAs (sf-cDNAs) were synthesized with a two-step amplification system by use of our modified Degenerate Oligonucleotide Primed Shuttle Polymerase Chain Reaction (DOP-Shuttle-PCR) method. The sf-cDNAs were hybridized onto RNase A treated metaphases from K562, and the ABRs were microdissected and reamplified with DOP-Shuttle-PCR primer-II. The reamplified sf-cDNAs were cloned into a pBluescript vector. Twenty randomly chosen clones were sequenced and classified into 8 groups. Three out of the 8 grouped clones had been mapped to the long arm of chromosome 22 (22q11), whereas the other 5 were novel cDNAs. Quantitative Southern blot analysis indicated that 7 out of the 8 grouped clones (87.5%) were derived from the co-amplified regions.
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PMID:Microdissection-mediated selection of chromosome region-specific cDNAs. 928 14

We examined homozygous deletion, point mutation and expression of DPC4 gene, a recently isolated candidate pancreatic tumor suppressor gene, in 53 patients with myelogenous leukemias and 5 cell lines. The patients consisted of 34 cases of chronic myelogenous leukemia including 22 in the chronic phase, 3 in the accelerated phase, and 9 in blastic crisis, and 19 with acute myelogenous leukemia including 9 at the initial presentation and 10 at relapse. Polymerase chain reaction (PCR)-based deletion analysis for DPC4 exon 8 and PCR-single strand conformation polymorphism study for the entire coding region were carried out. Homozygous deletion or subtle mutation was not detected in any of the samples examined. However, 3 patients with various clinical phases showed a decrease of DPC4 expression. These results suggest that DPC4 alteration is not a crucial event in the development or the progression of myelogenous leukemias.
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PMID:Rare alteration of genomic structure or expression of the DPC4 gene in myelogenous leukemias. 964 95

We established two novel PH-positive acute leukemia cell lines with "biphenotypic" feature, NALM-27 and NALM-28, with t(9;22;10)(q34;q11;q22) from a patient with biphenotypic acute leukemia(BAL). The breakpoint cluster region (bcr) of the BCR gene was found to be rearranged in these cells by Southern blot analysis using a major 3'-side bcr probe. Polymerase chain reaction (PCR) results showed differences in the pattern of expression of the abl-bcr fusion gene in comparison with the diagnosis. In the case of variant Ph translocations, reports have appeared concerning mainly chronic myelogenous leukemia (CML), but there have been few concerning acute leukemia with lymphoid feature. This study thus identifies nonrandomly involved chromosome sites which can then be targeted for detailed molecular analysis to obtain an understanding of abl-bcr fusion in the cells with lymphoid feature. In addition, chromosome band 10q22, involved in this translocation, is the site for several neoplasia. Furthermore, this site is non-randomly involved in the formation of variant Ph translocations in acute lymphoblastic leukemia (ALL). This is the first report on the t(9;22;10)(q34;q11;q22) rearrangement in NALM-27 and NALM-28 cell lines which should prove useful for understanding the translocation of molecular breaks within the bcr of the complex translocation site.
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PMID:Establishment and characterization of "biphenotypic" acute leukemia cell lines with a variant Ph translocation t(9;22;10) (q34;q11;q22). 971 Jul 20

Immunophenotypic studies have a limited role in the diagnosis of chronic myelogenous leukemia (CML) but are increasingly being used in CML blast transformation (BT). Determination of the cell lineage of CML blasts is clinically important because patients with lymphoid blast transformation have a better response to chemotherapy and longer survival than those with other lineages. We studied the morphologic, cytochemical, immunophenotypic, cytogenetic, and molecular features of 20 patients with Philadelphia chromosome-positive CML and more than 10% blast cells in peripheral blood or bone marrow. The blasts were morphologically heterogeneous. CD33 was expressed in 19 cases (95%), followed by CD13 (85%), CD11c (80%), CD36 (60%), CD117 (40%), and CD15 (30%). Seven cases (35%) had a precursor-B lymphoid immunophenotype, and 13 (65%) had a predominantly myeloid immunophenotype. Of the former group, of which only one had a pure lymphoid phenotype, terminal deoxynucleotidyl transferase (TdT) and CD19 were expressed in 100%, CD10 in 85.7%, and CD20 in 14.3%. Of the latter group, all 13 expressed from 3 to 6 myeloid antigens, with 46.2% myeloperoxidase positive and 69.2% CD61 positive. No cases were interpreted as T lineage, but the T-cell antigens CD3, CD4, CD5, and CD7 were expressed in 5.0, 40.0, 5.3. and 30.0% of all cases, respectively. In most cases, the immunophenotype of the CML blasts could not be predicted from their morphologic features. Polymerase chain reaction showed that 80.0% of the lymphoid group and 37.5% of the myeloid group had immunoglobulin heavy-chain gene rearrangements. The frequent lineage infidelity of the blast cells in CML BT seems to be related to the stem cell origin of this disorder. Such lineage infidelity, however, makes classification of many cases difficult and the significance of and criteria for biphenotypic blast crisis of CML is yet to be determined.
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PMID:The immunophenotype of blast transformation of chronic myelogenous leukemia: a high frequency of mixed lineage phenotype in "lymphoid" blasts and A comparison of morphologic, immunophenotypic, and molecular findings. 987 54

Polymerase chain reaction (PCR) is a powerful and rapid method for specifically detecting BCR-ABL rearrangement by amplification of the complementary DNA (cDNA) produced by reverse transcription of BCR-ABL mRNA. We studied 29 patients for detecting the presence of BCR-ABL transcripts before and after bone marrow transplantation (BMT). Our sample was composed of two different groups of patients: one group (n = 18) was studied by serial follow-ups before and after BMT; a second group (n = 11) was studied several years after BMT. Detection of BCR-ABL was carried out with different primer sets at different periods of the clinical outcome of chronic myeloid leukaemia (CML). A comparison of PCR data and clinical-haematological conditions showed clear differences between patients. In the first group, eight patients showed a positive correlation between a favourable clinical outcome and molecular remission. Conversely, in the second group, six patients were BCR-ABL positive between 20 and 117 months after BMT, while only two of these patients showed signs of clinical relapse. Among all patients whose isoforms were known at some time during the course of CML, the more frequent isoform was b3a2. These results were compared to previous findings in the literature on diagnosis, outcome and prognosis of CML.
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PMID:Detection of BCR-ABL transcripts in chronic myeloid leukaemia by nested PCR. 1007 Nov 34

Molecular diagnostic tests are widely performed in managing hematologic malignancies such as leukemia and lymphoma. In this article, we review the present application and problems of the tests. Karyotyping is performed at diagnosis of all kinds of hematologic malignancies. This method needs dividing cells as samples and skilled experts. Fluorescence in situ hybridization(FISH) analysis using cells in interphase is performed, for example, to monitor the effect of interferon on chronic myelogenous leukemia patients. The weak point of this method is that approximately 2% of false-positive cells are inevitable. Southern blot method is used for clonal analysis in some disease, for example, adult T-cell leukemia/lymphoma. Polymerase chain reaction(PCR) method using genomic DNA is performed for limited types of diseases such as lymphoma with bcl-2/IgH fusion gene. Reverse transcription(RT)-PCR method can detect fusion gene transcripts with high sensitivity. This method is useful for detecting minimal residual diseases after chemotherapy or bone marrow transplantation. To perform quantitative analysis, real-time PCR or competitive PCR must be done. In the near future, new technology such as gene expression profiling analysis using DNA microarrays or spectral karyotyping(SKY) method will be used in clinical practice.
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PMID:[Molecular diagnostic tests in hematologic diseases]. 1130 16

We investigated the polymorphic CAG-repeat distribution and the X-inactivation status of the human androgen receptor (HUMARA) gene in 58 female Japanese volunteers. Polymerase chain reaction amplification was performed using a fluorescent-dye-labeled primer under conditions specific for GC-rich targets, and fragments were analyzed. To estimate the length of these fragments, FAM-labeled (blue fluorescent) products were simultaneously compared with ROM-labeled size markers (red) that were created by sequencing various HUMARA fragments. The number of polymorphic CAG repeats of HUMARA in 116 alleles from 58 female subjects ranged from 15 to 28. Of the 58 volunteers, 51 (88.0%) were heterozygous. In 96% of the heterozygous female subjects, the allelic differences were no greater than 6 repeats. X-chromosome inactivation was calculated as the ratio of the area of the smaller peak to the sum of the areas of the smaller and larger peaks. The average ratio was 0.38 (range, 0.09-0.50). Preferential use of 1 allele, by more than 75% (ratio. <0.25). was observed in 5 volunteers (10.9%). The clonal nature of a patient with chronic myelogenous leukemia was easily identified. This method is sensitive enough to discriminate a difference of 1 triplet repeat.
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PMID:Analysis of the distribution of CAG repeats and X-chromosome inactivation status of HUMARA gene in healthy female subjects using improved fluorescence-based assay. 1172 64


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