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首页> 外文期刊>british journal of haematology >Generation of activated natural killer (A‐NK) cells in patients with chronic myelogenous leukaemia and their role in thein vitrodisappearance of BCR/abl‐positive targets
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Generation of activated natural killer (A‐NK) cells in patients with chronic myelogenous leukaemia and their role in thein vitrodisappearance of BCR/abl‐positive targets

机译：Generation of activated natural killer (A‐NK) cells in patients with chronic myelogenous leukaemia and their role in thein vitrodisappearance of BCR/abl‐positive targets

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Activated natural killer (A‐NK) cells, a subset of CD56dimCD3–lymphocytes, are obtained from PBMC of normal donors by adherence to plastic and culture in the presence of IL2. In this study we tested the feasibility of generating A‐NK cells in patients with Ph+chronic myeloid leukaemia (CML). Cultures obtained from patients with early chronic phase (ECP;n=7) contained a mean (±SD) of 83 ± 7 of CD56+CD3–cells, and those from patients with advanced chronic phase (ACP;n=7) contained 27 ± 33 CD56+CD3–cells. In three patients with leukaemia in a blastic phase (BP) it was only possible to obtain one culture enriched in CD56+CD3–cells (81). Cellular aggregates of myeloid cells and large granular lymphocytes were observed in early A‐NK cell cultures. Paired freshly‐adherent and cultured A‐NK cells were tested for the presence of BCR/abl mRNA by RT‐PCR. The BCR/abl+cells were detected in all 12 preparations of the freshly adherent A‐NK cells tested. In 6/12 the BCR/abl+cells were no longer detectable by RT‐PCR on day 14 of culture. Both proliferation and antileukaemic cytotoxicity were significantly higher (P= 0.002 andP= 0.029, respectively) in the BCR/abl–cultures than those in the six BCR/abl+cultures. 5/6 BCR/abl–cultures were highly enriched in A‐NK cells on day 14, and 1/6 contained predominantly CD56+CD3+cells. Only 2/6 BCR/abl+cultures were enriched in A‐NK cells on day 14, but they had poor cytotoxicity and a low proliferative index. Myeloid cells (CD33+) were more frequently detected in the BCR/abl+than BCR/abl–A‐NK cell cultures (P= 0.028). These observations suggest that: (1) populations of benign A‐NK cells can be generated from the peripheral blood of CML patients; (2) the ability to generate A‐NK cells is impaired in patients with advanced CML; and (3) the ability to generate A‐NK cells with antileukaemic activity correlates with th

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