X-chromosome inactivation patterns using HPRT and PGK polymorphisms in haematologically normal and post-chemotherapy females.
Clonal analysis using X-chromosome inactivation patterns of the hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) genes has been used in the assessment of haematological malignancies. In many analyses normal haemopoietic tissue or constitutive DNA from each individual has not been readily available and it has been assumed that when the ratio of the percentage of the two alleles remaining after differential methylation enzyme digestion is greater than 3/1 then an oligoclonal/monoclonal population of cells is present. We report here in a study of 65 haematologically normal females informative for HPRT or PGK that 15 (23%) had a skewed Lyonization pattern with clonal analysis ratios greater than 3/1. No correlation was observed between age and the X-chromosome inactivation pattern to suggest the detection of pre-malignant clonal states. The incidence was similar in 23 females who had received conventional combination chemotherapy, with six women (26%) having a ratio greater than 3/1. In the majority of individuals therefore, conventional chemotherapy does not appear to alter the patient's X-chromosome inactivation pattern. These results indicate that caution must be exercised in interpreting the results of clonal analysis of any given individual.
Gale
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RE
Department of Haematology, University College and Middlesex School of Medicine, London.
Wheadon
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H
Linch
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DC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004247:DNA / Q000032:analysis; D004303:Dosage Compensation, Genetic; D005260:Female; D006579:Heterozygote; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008223:Lymphoma / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D010735:Phosphoglycerate Kinase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics
D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D010735:Phosphoglycerate Kinase