title: Frequency of clonal remission in acute myeloid leukaemia.
abstract: 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.
authors.affiliation: Department of Haematology, University College London Medical School, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Gale
authors.forename: H
authors.initials: H
authors.lastname: Wheadon
authors.forename: A H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells; D016022:Case-Control Studies; D002999:Clone Cells; D004303:Dosage Compensation, Genetic; D005260:Female; D006098:Granulocytes; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000628:therapy; D008875:Middle Aged; D012074:Remission Induction