Significance of chemokine receptor expression in aggressive NK cell leukemia

Abstract

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.

Novel Role for Interleukin-2 Receptor-Jak Signaling in Retrovirus Transmission

“…Finally, the cells are removed from the top of the membrane, and the migratory cells are stained and quantified. The migration distance through the filter was measured in micrometers using the leading-front technique as previously described (40). Our data demonstrate that p12 expression increased the ability of cells to migrate through filters (Fig.…”

“…Cell migration was assessed essentially as described previously (40,71). Cells were incubated in the absence of IL-2 for 4 h and then added to the top of a 5-m polycarbonate membrane (Neuro Probe, Inc.) soaked with 10 g/ml ICAM (R&D Systems) in a chemotaxis chamber containing various amounts of IL-2 in the lower chamber.…”

Antagonism of CXCR3 Inhibits Lung Metastasis in a Murine Model of Metastatic Breast Cancer

“…CXCR4 expressed by tumor cells may also interact with CXCL12 to facilitate tumor growth and escape from oxygen starvation-induced apoptosis (3)(4)(5)(6)(7). In several malignancies, tumor cell expression of chemokine receptors is associated with more aggressive disease and poorer prognosis (8)(9)(10)(11). Similar to CXCR4, CXCR3 has now been identified in a variety of malignant cells, including melanoma, breast and prostate carcinomas, neuroblastoma, and a subset of B cell lymphomas (12)(13)(14)(15)(16)(17).…”

Aggressive Mature Natural Killer Cell Neoplasms: from Disease Biology to Disease Manifestations

“…Previous studies revealed that ANKL cells are positive for CXCR1 and CCR5, whose major ligands are CXCL8 (interleukin-8, IL-8) and CCL3 (MIP-1alpha, macrophage inflammatory protein type 1 alpha), CCL4 (MIP-1beta) and CCL5 (RANTES, regulated on activation, normal T cell expressed and secreted), respectively [128]. In addition, the serum level of IL-8, MIP-1alpha and MIP-1beta, are significantly elevated in ANKL patients and ANKL cells are positive for IL-8, MIP-1alpha, MIP-1beta and RANTES [129].…”

“…These include genes codifying for matrix metallopeptidases and their inhibitors, cathepsins and chemokines, among others [114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129].…”