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

Departments of ¹ Haematology/Oncology and ² Pediatric Haematology/Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and ³ First Department of Internal Medicine, Chiba University School of Medicine, Chiba, Japan

Requests for reprints: Arinobu Tojo, Department of Haematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato, Tokyo 108-8639, Japan. Phone: 81-3-5449-5633; Fax: 81-3-5449-5429; E-mail: a-tojo{at}ims.u-tokyo.ac.jp.

Purpose: 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.

Key Words: CD34 • CD7 • BCR-ABL • CML • Leukemias and lymphomas • Laboratory correlates

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