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2016 ; 7
(ä): 454
Nephropedia Template TP
Sánchez-Martínez D
; Lanuza PM
; Gómez N
; Muntasell A
; Cisneros E
; Moraru M
; Azaceta G
; Anel A
; Martínez-Lostao L
; Villalba M
; Palomera L
; Vilches C
; García Marco JA
; Pardo J
Front Immunol
2016[]; 7
(ä): 454
PMID27833611
show ga
Mutational status of TP53 together with expression of wild-type (wt) IGHV
represents the most widely accepted biomarkers, establishing a very poor
prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell
therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as
an effective and safe alternative in the treatment of acute myeloid and lymphoid
leukemias that do not respond to traditional therapies. We have described that
allogeneic activated NK cells eliminate hematological cancer cell lines with
multidrug resistance acquired by mutations in the apoptotic machinery. This
effect depends on the activation protocol, being B-lymphoblastoid cell lines
(LCLs) the most effective stimulus to activate NK cells. Here, we have further
analyzed the molecular determinants involved in allogeneic NK cell recognition
and elimination of B-CLL cells, including the expression of ligands of the main
NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present
preliminary data suggesting that B-CLL susceptibility significantly correlates
with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that
the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53
and IGHV mutational status. Cells from patients with worse prognosis (mutated
TP53 and wt IGHV) are the most susceptible to activated NK cells. Hence, B-CLL
prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK
cell transfer represents a good alternative to treat poor prognosis B-CLL
patients who present a very short life expectancy due to lack of effective
treatments.