CD34+CD7+ Leukemic Progenitor Cells May Be Involved in Maintenance and Clonal Evolution of Chronic Myeloid Leukemia

Abstract

AbstractPurpose: We analyzed CD34+ cells coexpressing CD7 in chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase (AP) to clarify their role in progression or regression of the disease during treatment.Experimental Design: Enumeration of CD34+CD7+ cells was done on bone marrow nucleated cells from normal donors and CML patients. Fluorescence in situ hybridization analysis was done on sorted CD34+CD7+ and CD34+CD7− cells to examine the occupancy rate of each fraction by BCR-ABL+ cells with or without additional cytogenetic abnormalities.Results: The proportion of CD34+CD7+ cells was significantly affected by the treatment outcome and/or the disease status as follows: 20.5 ± 10.4% in normal donors (n = 22), 18.1 ± 10.2% in CP with major cytogenetic response (n = 14), 53.0 ± 12.9% in CP at diagnosis (n = 18), 55.0 ± 15.8% in CP with minor or no cytogenetic response (n = 28), and 70.2 ± 18.1% in AP (n = 6). The proportion of CD34+CD7+ cells decreased in parallel with cytogenetic improvement in individual patients. In six untreated CP patients, the ratio of BCR-ABL+ cells was comparable between each fraction. In three patients with major cytogenetic response, the ratio of BCR-ABL+ cells was remarkably lower in CD34+CD7− cells than in CD34+CD7+ cells. In three AP patients with additional cytogenetic abnormalities, extra signals were detected at a much higher rate in CD34+CD7+ cells than in CD34+CD7− cells.Conclusions: Our results suggest that CD34+CD7+ cells may be involved in maintenance and clonal evolution of BCR-ABL+ cells in CML.