Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia

IL-1 -releasing human acute myeloid leukemia blasts modulate natural killer cell differentiation from CD34+ precursors

“…[12][13][14][15] In this context, it has been shown that sera derived from human AML patients may haematologica 2015; 100:e44 14 This effect was not detectable under our experimental condition, most likely due to the use of a trans-well system in which microvescicles cannot diffuse from upper to lower chambers containing cell precursors. Notably, previous reports regarding inhibitory AML-mediated effect focused on PB mature NK cells, and not on differentiating NK-cell precursors, which may display a different susceptibility to AML-derived inhibitory factors.…”

Impaired cytotoxicity associated with defective natural killer cell differentiation in myelodysplastic syndromes

“…Notably, similar analyses of NK cells in patients with acute or chronic myeloid leukemia revealed no such changes of the CD56 bright and CD56 dim subsets, suggesting that the underlying mechanisms are specific to MDS. 30,31 We did not detect a significant increase in spontaneous apoptosis of CD56 dim and CD56 bright NK cells in MDS patients, making it unlikely that the observed lack of mature NK cells is due to selective cell death of the CD56 dim NK cell subset (Online Supplementary Figure S5). One possibility that was not thoroughly addressed in this study is that the malignant clone contributes to altered NK cell differentiation of NK cell progenitors.…”

MicroRNA-29b mediates altered innate immune development in acute leukemia

“…NK cells in AML patients can have a reduction in NKP30-, NKP44-, and NKP46-activating receptors that can lead to decreased NK cell cytotoxicity against AML blasts (8,29,30,35). The inhibitory receptor NKG2A has also been demonstrated to be upregulated on NK cells from AML patients, and is associated with failure to reach remission (34). Additionally, AML blasts can evade NK cells by shedding activating stress ligands such as MICA and MICB, which, once soluble, can activate NK cell activity away from the actual tumor cell and lead to innate immune exhaustion (9,36).…”