Evaluation of clonality in myeloid stem-cell disorders

Clonality in myeloid stem-cell disorders can be determined using either indirect methods such as analysis of X-chromosome inactivation patterns (XCIPs), or detection of specific abnormalities such as the chromosomal translocations characteristic of myeloid leukemias. XCIPs are particularly useful for disorders lacking evidence of a specific marker. Most females can be studied using polymerase chain reaction (PCR) analysis of differential DNA methylation patterns in the human androgen receptor (HUMARA) or phosphoglycerate kinase (PGK) genes, and approximately 68% can be studied using transcription assays of three polymorphic genes, glucose-6-phosphate dehydrogenase (G6PD), iduronate-2-sulfatase (IDS), and p55. Studies are limited by the incidence of constitutive and acquired (age-related) skewing and results must be carefully interpreted with reference to appropriate control samples. These techniques have been applied to clonality status of hematological disorders, lineage involvement in a clonal process, and detection of clonal evolution.