Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some patients with an early or latent myeloproliferative disorder (MPD) present with Budd-Chiari syndrome (BCS, hepatic vein thrombosis). Cell culture analysis of erythroid progenitors (BFU-E) can be used to discriminate primary from secondary MPD and examination of X-chromosome inactivation (in females) can be used to demonstrate clonality in neoplastic tissues. The present study used these techniques to examine whether a group of 7 female patients who presented with BCS had evidence to support a diagnosis of MPD. Unilateral X-inactivation and therefore clonality can be studied in females heterozygous for X-linked restriction fragment length polymorphisms (RFLP) by differences in methylation between active and inactive chromosomes. Probes for two polymorphic loci, phosphoglycerate kinase (PGK, at Xq13.3 [BstX1 RFLP]) and M27 beta (an anonymous locus DXS255 at Xp11.22 [Pst1 RFLP]) were used to study methylation patterns. All 7 patients were heterozygous using M27 beta and 2/7 were also heterozygous using the PGK probe. Polyclonal patterns of X-inactivation in granulocytes were demonstrated in 3/7, a skewed/monoclonal pattern in 1/7 and aberrant patterns in 3/7 using M27 beta. Two patients who had aberrant patterns of X inactivation with M27 beta demonstrated a skewed/monoclonal pattern with PGK. The results of BFU-E growth patterns and clonality were entirely concordant in 5/6 patients. Thus X-chromosome inactivation patterns, in conjunction with erythroid colony studies, can be used to assist in the diagnosis of an underlying MPD in BCS.
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PMID:Identification of latent myeloproliferative disease in patients with Budd-Chiari syndrome using X-chromosome inactivation patterns and in vitro erythroid colony formation. 749 78

The unusual case of myeloproliferative disease described here is characterized by the following features: (1) a clinically completely silent course for 11 years without splenomegaly, marrow fibrosis, or cellular morphologic alterations; (2) the presence, at the onset, of a Philadelphia (Ph) chromosome without DNA breakpoints in the M-bcr region; (3) the spontaneous loss of detectable Ph-positive cells, 5 years after the first finding of leukocytosis, in the absence of any therapy; (4) the maintenance of the clonal nature of hematopoiesis, as revealed by the PGK X-linked inactivation pattern, in the absence of the Ph chromosome; and (5) a biphasic trend in the levels of leukocytes, red cells, and platelets during the years of observation.
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PMID:Spontaneous loss of Ph chromosome with maintenance of clonal hemopoiesis in an untreated patient with myeloproliferative disease and a long survival. 753 65

Clonal haemopoiesis has previously been demonstrated in some 30% of patients in remission of acute myeloid leukaemia (AML). Whilst a 'clonal remission' in many such patients may represent a skewed X-chromosome inactivation pattern in haemopoietic cells, its relationship to an underlying preleukaemic state remains uncertain. We therefore analysed the clonal status of 48 female patients in remission of AML using X-chromosome linked restriction fragment length polymorphisms (RFLPs) within the X-linked PGK and HPRT genes and the DXS255 (M27 beta) locus, and carried out in conjunction a detailed study of the morphological and karyotypic features of the patients' bone marrows. During remission, 35 patients (73%) with AML demonstrated nonclonal haemopoiesis, and their bone marrows were morphologically normal. Remission haemopoietic tissue in nine cases (19%) showed a skewed X-chromosome inactivation pattern and remission bone marrows in these patients had features of trilineage myelodysplasia (TMDS), with seven having similar features at presentation. Analysis of constitutional DNA showed a non-clonal pattern in seven of these patients, but was unsuccessful in two cases. These nine patients with post-chemotherapy TMDS were considered to have true clonal haemopoiesis. Four patients (8%) with a skewed X-chromosome inactivation pattern had normal remission bone marrows. Analysis of constitutional DNA showed a skewed pattern in two of these patients, but was unsuccessful in two cases. Cytogenetic investigation during remission in the nine patients with TMDS showed a normal karyotype in four cases and the acquisition of new karyotypic abnormalities in three cases. In contrast, 10 female patients in remission of de novo acute lymphoblastic leukaemia (ALL) were shown to have non-clonal haemopoiesis. We conclude that the majority of patients with AML who achieve remission after cytoreductive chemotherapy have non-clonal haemopoiesis, and when clonal remissions are observed these are commonly associated with the development of trilineage myelodysplasia in the bone marrow, with or without karyotypic abnormalities. True clonal remission in association with morphologically normal haemopoiesis is a rare entity, the significance and frequency of which remain uncertain.
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PMID:Clonal remissions in acute myeloid leukaemia are commonly associated with features of trilineage myelodysplasia during remission. 791 32

Phosphoglycerate kinase (EC 2.7.2.3; PGK) exists in two forms in marsupials. PGK1 is an X-linked house-keeping enzyme, and PGK2 is a mainly testis-specific enzyme under autosomal control. We have used PGK1 probes derived from two closely related species of macropodid marsupials (kangaroos and wallabies) to demonstrate the existence of a large family of pseudogenes in the tammar wallaby (Macropus eugenii). Over 30 fragments are detectable after Taq digestion. We estimate that there are 25-30 copies per genome. Most are autosomally inherited and are apparently not closely linked. Only two restriction fragments that appeared to be sex linked could be detected. Varying degrees of hybridization of fragments to the probes suggest different levels of homology, and hence different ages of origin. The existence of two PGK1 homologous restriction fragments from the X and a large number from the autosomes was also demonstrated by somatic cell hybridization for two other macropodid species, the wallaroo (M. robustus) and the red kangaroo (M. rufus). These results are compared with those from human and mouse, and it is suggested that the propensity of PGK1 to form pseudogenes is an ancient (approximately 130 MYR BP) characteristic of mammals. The high level of polymorphism detected in the tammar makes these PGK1 probes potentially useful for measuring genetic variability in this species and other macropodids.
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PMID:Phosphoglycerate kinase pseudogenes in the tammar wallaby and other macropodid marsupials. 800 Jan 35

Analysis of X-chromosome inactivation patterns in females has been used to assess clonality of various tumours and for prenatal diagnosis of X-linked disorders. Studies with these methods in acute myeloid leukaemia suggest that a significant proportion of cases have clonal remissions (ie, persistence of the malignant clone), which may represent return to a preleukaemic state. We therefore analysed X-chromosome inactivation patterns with differential methylation patterns of heterozygotes for three DNA probes, HPRT, PGK, and M27 beta, in leukaemic patients and normal controls. As expected, blast cells from 67 of 68 analysable samples (99%) were monoclonal or had a skewed X-inactivation pattern. A skewed pattern in remission was also found in 26 of 77 patients (34%), proportion only slightly greater than control (16/75, 21%). In 7 of 10 patients with a skewed pattern in myeloid cells there was similar skewing in the T cells, which is compatible with the concept of a constitutively skewed X-chromosome inactivation pattern of haemopoietic cells in these patients. Our study illustrates the difficulty of interpreting clonality in individual tumour samples and emphasises the importance of comparisons with non-malignant tissue of the same cell type from that individual and from normal control populations.
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PMID:Frequency of clonal remission in acute myeloid leukaemia. 809 44

Clonality analysis, by means of polymorphisms of X-linked genes and their methylation patterns, was performed in 41 female patients with various types of refractory anemia. Bone marrow cells, peripheral blood cells, and granulocytic and lymphocytic fractions were analysed by Southern blotting with PGK, HPRT, and M27 beta probes. Clonal hematopoiesis was evidenced in 8 of 19 patients with aplastic anemia, 4 of 6 patients with RA or RARS, 3 of 7 patients with PNH, and 5 of 9 patients whose hematological characteristics did not meet the criteria of either of these entities. For aplastic anemia, clonal hematopoiesis was demonstrated in higher frequency in the patients who had longer history after diagnosis. In refractory anemia, as a whole, no clear correlation was observed between existence of clonal hematopoiesis and morphological characteristics of hematological cells.
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PMID:[Clonality in refractory anemia]. 809 42

The lymphoproliferative disease of granular lymphocytes (LDGL) results from chronic proliferation of either CD3- or CD3+ large granular lymphocytes (LGLs). Most CD3+ LGLs have been well characterized as clonal LGL proliferations (LGL leukemia). In contrast, the clonal nature and clinical features of patients with CD3- LDGL have not been defined. In this study, we analyzed seven female patients with CD3- LDGL who were heterozygous at certain X-linked gene loci. Neutrophils and CD3- granular lymphocytes were isolated from peripheral blood. Clonal analysis was performed on genomic DNA from these cell fractions on six patients by conventional Southern techniques using probes to the X-linked genes, PGK and DXS255 (M27 beta). In four patients, three of whom were already studied by Southern analyses of genomic DNA and one in whom there were insufficient amounts of DNA, polymerase chain reaction (PCR)-based clonal analysis was performed with primer pairs flanking the BstXI polymorphism on the PGK gene. In six patients, a polyclonal expansion of CD3- granular lymphocytes was demonstrated and in one the result was indeterminate. In contrast to patients with CD3+ LDGL (LGL leukemia), a clonal disease could not be demonstrated with X-linked markers in patients with CD3- LDGL, suggesting a reactive rather than a neoplastic origin of the lymphocytes in these cases.
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PMID:Clonal studies of CD3- lymphoproliferative disease of granular lymphocytes. 809 33

We studied 98 female patients in remission (2-240 months) from childhood ALL to determine the clonality status of their hematopoiesis. Thirty-one (31.6%) were heterozygous at the PGK locus for the BstX1 endonuclease restriction site, permitting X-linked clonality assays to be performed. Two patients were in relapse at the time of study and were excluded. We used the PGK-PCR clonality assay (PPCA) to analyze DNA from PMN and mononuclear cells of the remaining 29 female patients. All (29/29) patients demonstrated polyclonal hematopoiesis. These data show that remission from childhood ALL involves reestablishment of polyclonally derived hematopoiesis in all patients studied.
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PMID:Clonality analysis of childhood ALL in remission: no evidence of clonal hematopoiesis. 810 90

Clonality of archival formalin-fixed tissue sections was analyzed by polymerase chain reaction amplification of a portion of the X-linked phosphoglycerate kinase (PGK-1) gene. Amplification was successful in 29 of 36 cases of uterine endometrioid adenocarcinoma. Five of these cases, including both tumor and control tissue from the same patients, were heterozygous for the BstXI polymorphic site of the PGK-1-amplified product, permitting analysis of clonality. Pretreatment of the DNA with HpaII blocked amplification of one of the two PGK-1 alleles from four of five cases of tumor, indicating the clonal pattern of X chromosome inactivation in these cases. In contrast, in DNA from paired control tissues HpaII pretreatment had no effect, indicating a random pattern of X chromosome inactivation in normal tissue. One of the cases of endometrioid adenocarcinoma contained a high proportion (45%) of nontumor cells, precluding the determination of clonality. We conclude that polymerase chain reaction amplification can be used for the determination of the pattern of X chromosome inactivation in formalin-fixed tissue sections. Such an approach makes it feasible to include specimens from archival tissue collections in the analysis of clonality.
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PMID:Analysis of clonality in archival tissues by polymerase chain reaction amplification of PGK-1. 815 Apr 59

Using a variety of genetic methods, it is shown in this paper that the genes GLA, G6PD, HPRT, and PGK are X-linked in the vole Microtus subarvalis. The order of these genes has been investigated in two vole species, M. subarvalis and M. kirgisorum, by using the mapping technique of Goss and Harris (1977a, b), which depends on the analysis of gamma-ray-induced gene segregation. The experimental data were processed with the computer programme RHMAP (Ginsburg et al., 1993). The analysis indicated that the correct gene order in M. subarvalis is PGK-HPRT-G6PD-GLA, and the same gene order was found to be the most probable for M. kirgisorum. The relative distances between the genes in the two vole species are apparently the same. The RHMAP programme has also been applied to data previously reported for the same set of X-linked genes in the American mink (Zhdanova et al., 1988), the Australian marsupial Planigale maculata (Dobrovic and Graves, 1986), and man. The evolutionary conservation of the linear order of these X-linked genes in different mammalian taxa is discussed.
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PMID:Demonstration of the X-linkage and order to the genes GLA, G6PD, HPRT, and PGK in two vole species of the genus Microtus. 825 99


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