Detection of minimal residual disease and relapse remain major problems in chronic myelogenous leukemia (CML) patients following bone marrow transplantation (BMT). In order to disclose the 9;22 Philadelphia translocation, we used a fluorescence in situ hybridization (FISH) technique. BCR and ABL gene fragments were used as probes for the detection of the BCR/ABL fusion product in peripheral blood and bone marrow cells from 11 CML patients in which 5 were post-BMT. The sensitivity and specificity of this approach were compared to conventional cytogenetic and polymerase chain reaction (PCR) methods. FISH demonstrated a high degree of sensitivity (1%) for the detection of the BCR/ABL translocation in these patients. A linear correlation was found between FISH detection of the BCR/ABL fusion product and routine chromosomal analysis (r = 0.995; p < 0.001). Detection of the BCR/ABL signal by FISH was observed in all patients showing a positive PCR signal. A significant reduction in BCR/ABL signal was observed post-transplant (p < 0.001). However, the BCR/ABL translocation was detected in four of five transplanted patients immediately (0.75-2.5 months) following transplant and was found in patients with a low expression of the translocation.
Bibliographical noteFunding Information:
The authors are indebted to Drs. P. Drakos, D. Meitis, M. Lishner, M, Mitelman, and A. Eldor for referring to us the patients included in the study. We thank A. Ackerstein, E. Blumenthal, A. Sweed, and R. Condiotti for excellent assistance. The superb care given by the medical staff in the Department of BMT at Hadassah University Hospital was greatly appreciated. These findings were presented in part at the American Society of Human Genetics, San Francisco, November, 1992.