~~56+bright and CD56+d'm Natural Killer Cells in Patients With Chronic Myelogenous Leukemia Progressively Decrease in Number, Respond Less to Stimuli That Recruit Clonogenic Natural Killer Cells, and Exhibit Decreased Proliferation on a Per Cell Basis

Human natwral killer cells (NK) require accessory cell-derived contact and soluble factors for maximal expansion. However, it is unclear whether increased recruitment of clonogenic NK, increased proliferation on a per cell basis, or a combination of both is responsible for the increased expansion. We show that expansion of both CD56+d'm and CD56+""gM NK from normal donors is increased in the presence of M2-1084 accessory cell-soluble factors. In contrast, the addition of M2-1084 stromal ligands further augments only the expansion of CD56+b"gM NK. Using single-cell sorting of CD56+"gM NK, M2-lOB4-soluble and contact factors independemly increase both recruitment of clonogenic NK and proliferation on a per cell basis. This well-defined M21084 accessory cell system was used to investigate potential defects in NK from patients with CML. Although we have previously shown diminished interleukin-2 (IL-2)-activated NK outgrowth and function from patients with chronic myelogenous leukemia (CML) as their disease progresses, it has been unclear if this is due to a defect in an accessory cell function or an inherent abnormality of CML NK themselves. CD56+/CD3NK purified by fluorescence-activated cell sorting from 21 patients (7 early chronic phase [ECP] patients, 10 late chronic and accelerated phase [LCP/APl, and 4 blast crisis [BC] patients) were studied. The Proliferative capacity, clonogenic frequency, and cytotoxic capacity of CML NK were compared with NK from normal donors. The absolute number of circulating NK per milliliter of peripheral blood is