Clonality analysis using X-chromosome inactivation at the human androgen receptor gene (Humara). Evaluation of large cohorts of patients with chronic myeloproliferative diseases, secondary neutrophilia, and reactive thrombocytosis

Am J Clin Pathol. 1999 Jul;112(1):93-100. doi: 10.1093/ajcp/112.1.93.

Abstract

Chronic myeloproliferative diseases (MPDs) are not associated with consistent cytogenetic or molecular abnormalities. Demonstration of clonal cell growth by analysis of X-chromosome inactivation (XCI) patterns in females provides a promising tool for diagnosis. However, this technique can be complicated by excessive lyonization of normal cells mimicking clonal cell growth: We analyzed XCI patterns at the human androgen receptor (HUMARA) locus in 146 healthy females, 65 women with secondary neutrophilia, 31 women with reactive thrombocytosis, and 86 women with chronic MPDs. A skewed XCI pattern with greater than 75% amplification of 1 allele (allele ratio > 3:1) was found in 22 (9.1%) of 242 control subjects. The incidence of skewing was statistically significantly lower in women younger than 30 years (2/73) compared with women older than 60 years (10/53). Of 86 patients with a chronic MPD, 71 (82%) exhibited an allele ratio greater than 3:1, whereas only 10 (12%) of 86 age-matched control subjects showed a skewed XCI pattern. Although statistical evaluation of the data showed a significant difference between patients with a chronic MPD and control subjects, proof of clonality in individual, especially elderly, patients is difficult.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Chronic Disease
  • Clone Cells
  • Cohort Studies
  • DNA Primers / chemistry
  • Dosage Compensation, Genetic*
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukocytosis / genetics*
  • Leukocytosis / pathology
  • Middle Aged
  • Myeloproliferative Disorders / blood
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology
  • Neutrophils / pathology*
  • Polycythemia Vera / blood
  • Polycythemia Vera / genetics
  • Polymerase Chain Reaction
  • Primary Myelofibrosis / blood
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / pathology
  • Receptors, Androgen / genetics*
  • Thrombocytosis / blood
  • Thrombocytosis / genetics
  • Thrombocytosis / pathology

Substances

  • DNA Primers
  • Receptors, Androgen