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Danger signaling to NK cells in AML
their CRTLo counterparts (Figure 2B). To evaluate NK-cell effector functions in a more direct manner, we also per- formed NK-cell cytotoxicity assays using NK cell-sensi- tive human chronic myelogenous leukemia K562 cells as targets. In general, NK cells isolated from AML patients at
AB
recovery had slightly higher cytotoxic functions than NK cells isolated from AML patients prior to induction chemotherapy (Figure 2C). Importantly, while surface- exposed CRT failed to affect the ability of NK cells isolat- ed from AML patients prior to the initiation of treatment
P=0.03
P=0.04
Figure 1. The impact of ecto-CRT on natural killer (NK) cells and the levels of NK-cell ligands present on acute myeloid leukemia blasts. (A) The percentage and (B) absolute numbers of circulating CD45+CD3-CD56+ NK cells in CRTHi versus CRTLo acute myeloid leukemia (AML) patients before the induction chemotherapy (Prior, n=45) and at re-establishment of normal hematopoiesis (recovery, n=37) determined by flow cytometry. Boxplots: lower quartile, median, upper quartile; whiskers, minimum, maximum; ns: not significant. (C) The frequency of CD45+CD3-CD56+ NK cells staining positively for different NK cell receptors (namely NKp30, NKp46, NKG2D, NKp80, DNAM-1, CD16, CD158e1, CD158bj, CD158ah, NKG2A and ILT2) in CRTHi and CRTLo AML patients before the induction chemotherapy (prior, n=38) and at re-establishment of normal hematopoiesis (recovery, n=31) determined by flow cytometry. ns: not significant. (D) The percentage of CD45+CD33+ blasts stain- ing positively for NK cell ligands (MICA/B, ULBP, CD155 and CD112) in CRTHi versus CRTLo AML patients prior to the induction chemotherapy (n=21) determined by flow cytometry. Boxplots: lower quartile, median, upper quartile; whiskers, minimum, maximum; ns: not significant. CRT: calreticulin.
C
D
P=0.014
P=0.007
P=0.04
haematologica | 2020; 105(7)
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