Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload.

Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-1R signaling axis is involved in the pathogenesis of solid cancer, the role of this signaling pathway in hematological malignancy remains unknown. Here, we demonstrate that NK-1R expression is markedly elevated in the white blood cells from acute myeloid leukemia patients and a panel of human leukemia cell lines. Blocking NK-1R induces apoptosis in vitro and in vivo via increase of mitochondrial reactive oxygen species. This oxidative stress was triggered by rapid calcium flux from the endoplasmic reticulum into mitochondria and, consequently, impairment of mitochondrial function, a mechanism underlying the cytotoxicity of NK-1R antagonists. Besides anticancer activity, blocking NK-1R produces a potent antinociceptive effect in myeloid leukemia-induced bone pain by alleviating inflammation and inducing apoptosis. These findings thus raise the exciting possibility that the NK-1R antagonists, drugs currently used in the clinic for preventing chemotherapy-induced nausea and vomiting, may provide a therapeutic option for treating human myeloid leukemia.

[Analysis of scatter plots and alarm information in 288 cases of newly diagnosed hematologic malignancies].

This study was aimed to explore the role of full-automatic blood analyzer Sysmex XE-2100 in early screening and diagnosing the hematologic malignancies. A total of 288 samples of the patients with hematologic malignancies was examined. Then, the scatter plots, alarm information and blood smears were analyzed. The results indicated that 76% of these samples showed abnormal scatter plots. CMML and AML-M3 patients had their own characteristic scatter plots, while others hadnt's. The coincident rate of CMML and AML-M3 determined by scatter plots with practical diseases was 100%; the coincident rate of ALL determined by scatter plots with practical disease was 67%. The coincident rate of alarm information of blast cells was 92.5%, the coincident rate of immature granulocytes was 77.1%, the coincident rate of nucleated red blood cells was 33.3%, the coincident rate of atypical lymphocytes was 31.3%. It is concluded that the abnormal scatter plots and alarm information are very important for finding the patients with hematologic malignancies and determining the disease type. The alarm information has high reliability for blast cells and immature granulocytes, but has only mirror value for nucleated red blood cells and atypical lymphocytes.