Extensive cytogenetic studies of clonality following interferon-alpha therapy in chronic myeloid leukemia occurring in monosomic cells in a patient with Turner syndrome mosaic

In a 27-year-old female with Turner syndrome mosaic, Philadelphia (Ph) chro mosome-positive chronic myeloid leukemia (CML) occurred only in the monosom ic cells (45, Xc). Extensive cytogenetic studies, including triple-color fl uorescence in situ hybridization (FISH), revealed that Ph-positive monosomi c cells (45, Xc), Ph-negative monosomic cells and normal diploid cells (46, XX) were present in her bone marrow at diagnosis. After successful interfe ron therapy, the non-leukemia cells expanded and reconstituted normal hemat opoiesis resulting in complete cytogenetic response, following the selectiv e suppression of the monosomic Ph-positive leukemia clone. The ratio of Xc to XX cells in bone marrow cells was significantly increased to that in ski n fibroblasts. Moreover, the ratio of Ph-positive cells to Ph-negative cell s was found to be significantly different between karyotyping and FISH. Stu dies of this quite unique case not only confirmed the clonality of CML, eff ectiveness of interferon-alpha and X chromosome imbalance among different t issues, but also demonstrated a discrepant increase of the BCR/ABL-positive clone in CML. The latter supports the hypothesis that reduced programmed c ell death may be the primary mechanism responsible for the expansion of the leukemia clone in CML, Our study verifies the importance of extensive anal ysis of a neoplastic disease in patients with a constitutional chromosomal abnormality.