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

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

Twenty-nine patients with acute myelocytic leukemia (AML) and 14 patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were analyzed to detect the presence of mutations in their ras genes by the polymerase chain reaction and oligonucleotide hybridization methods. Deoxyribonucleic acid (DNA) isolated from blood or bone marrow samples was screened for mutations in codons 12, 13 and 61 of N-ras and in codons 12 and 61 of K-ras and H-ras. We detected mutations of the ras gene in 7 patients with AML (7/29), all in N-ras. The mutations were 3 GGT- greater than GAT transitions in codon 12, 1 GGT- greater than TGT transition in codon 13, and 3 CAA- greater than AAA transitions in codon 61. No correlation has been observed between French-American-British subtypes and the incidence of N-ras mutation, nor between cytogenetic changes and the incidence of N-ras mutation. All ras gene mutations detected by the oligonucleotide hybridization method were further confirmed by direct sequencing. No mutations were detected in ras genes in samples from the 14 Philadelphia chromosome-positive CML patients (12 in chronic phase, 2 in blastic phase). These findings are in line with previous results indicating that ras gene mutations in the codons tested play only a small role in the tumorigenesis of CML.
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PMID:Mutation analysis of the ras gene in myelocytic leukemia by polymerase chain reaction and oligonucleotide probes. 168 80

Since the introduction of interferon alpha-2b (IFN alpha-2b) into clinical oncology there have been several reports dealing with acute renal failure during therapy with this new type of anticancer drug. We investigated 58 patients (pts) with myeloproliferative syndromes (56 pts with chronic myelogenous leukemia, 2 pts with essential thrombocythemia) who were treated with 4 x 10(6) IU IFN alpha-2b each day subcutaneously. In order to assess the nephrotoxic potential we used the following noninvasive methods: 1. Analysis of the excretion of 4 urinary enzymes (LDH, LAP, GGT, NAG), 2. Determination of the excretion of protein, albumin, alpha-1-microglobulin immunoglobulin G (Ig G), 3. serum creatinine. The investigations were done every 2 weeks and took 70 weeks. We found an increase in the excretion of all 4 enzymes which remained stable during the whole observation period, protein excretion was pathological in about 20% of all pts and reached values of up to 9.07 g/L alpha-1-microglobulin was excreted in pathological amounts in about 20% of all pts during the whole observation period, albumin was found in pathological quantities in about 15% of all pts and Ig G was pathologically increased in the urine in about 10% of the pts. Serum creatinine rose in 5-10% of the pts up to 1.5 mg/dL. In conclusion, IFN alpha-2b is capable of inducing combined glomerular and tubular damage. Therefore, avoiding additional nephrotoxic insults is desirable.
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PMID:Investigations on the subclinical and clinical nephrotoxicity of interferon alpha-2B in patients with myeloproliferative syndromes. 195 45

A gene family encompassing a minimum of four genes or pseudogenes for gamma-glutamyl transferase (GGT; EC 2.3.2.2) is present on chromosome 22q11. We have previously isolated a cDNA related to GGT but clearly not belonging to its gene family. The chromosomal location of this related gene, GGTLA1, has been determined by both isotopic and fluorescence in situ hybridization to metaphase cells and by Southern blot analysis of somatic cell hybrid DNAs. We show that GGTLA1 is part of a distinct gene family, which has at least four members (GGTLA1, GGTLA2, GGTLA3, GGTLA4). At least two loci are located on chromosome 22 within band q11 and proximal to the chronic myelogenous leukemia (CML) breakpoint in BCR (breakpoint cluster region gene). At least one other member is located more distally between the breakpoints found in Ewings sarcoma and CML. Some of the GGT and GGTLA family members are located on NotI restriction enzyme fragments of a similar size. Combined results indicate that a segment of human chromosome 22q11 has undergone large-scale amplification events relatively recently in evolution.
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PMID:Localization of a gamma-glutamyl-transferase-related gene family on chromosome 22. 809 16