PMID- 23378843
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130205
LR  - 20211021
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 4
DP  - 2013
TI  - Cellular and molecular basis of haploidentical hematopoietic stem cell 
      transplantation in the successful treatment of high-risk leukemias: role of 
      alloreactive NK cells.
PG  - 15
LID - 10.3389/fimmu.2013.00015 [doi]
LID - 15
AB  - Natural killer (NK) cells are involved in innate immune responses and play a 
      major role in tumor surveillance and in defense against viruses. Human NK cells 
      recognize human leukocyte antigen (HLA) class I molecules via surface receptors 
      [killer immunoglobulin-like receptor (KIR) and NKG2A] delivering signals that 
      inhibit NK cell function and kill HLA class I-deficient target cells, a frequent 
      event in tumors or virus-infected cells. NK cell triggering is mediated by 
      activating receptors that recognize ligands expressed primarily on tumors or 
      virus-infected cells. NK cells play also a key role in the cure of high-risk 
      leukemias. Thus, donor-derived "alloreactive" NK cells are fundamental effectors 
      in adult acute myeloid leukemia and in pediatric acute lymphoblastic leukemia 
      patients undergoing haploidentical hematopoietic stem cell transplantation 
      (HSCT). Alloreactive NK cells mediate killing of leukemia cells and patient's 
      dendritic cell, thus preventing respectively leukemic relapses and graft-vs-host 
      responses. Cytofluorimetric analysis of KIRs expressed by NK cells allows to 
      define the size of the alloreactive NK subset and the selection of the best 
      potential donor. Recently, it has been shown that also the expression of 
      activating KIRs, in particular the (C2-specific) KIR2DS1, may contribute to donor 
      NK alloreactivity. It has also been established a correlation between the size of 
      the alloreactive NK cell population and the clinical outcome. Notably, the 
      alloreactive NK cells derived from donor's hematopoietic stem cells are generated 
      and persist in patients over time. The high survival rates of patients undergoing 
      haploidentical HSCT highlight an important new reality in the setting of 
      allograft performed to cure otherwise fatal leukemias. Novel approaches are in 
      progress to further improve the clinical outcome based on the infusion of donor 
      alloreactive NK cells either as a component of the transplanted cell population 
      or as in vitro expanded NK cells.
FAU - Locatelli, Franco
AU  - Locatelli F
AD  - Department of Pediatric Hematology/Oncology, Istituto Di Ricovero e Cura a 
      Carattere Scientifico, Ospedale Pediatrico Bambino Gesu Rome, Italy ; Universita 
      di Pavia Pavia, Italy.
FAU - Pende, Daniela
AU  - Pende D
FAU - Mingari, Maria C
AU  - Mingari MC
FAU - Bertaina, Alice
AU  - Bertaina A
FAU - Falco, Michela
AU  - Falco M
FAU - Moretta, Alessandro
AU  - Moretta A
FAU - Moretta, Lorenzo
AU  - Moretta L
LA  - eng
PT  - Journal Article
DEP - 20130201
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC3561663
OTO - NOTNLM
OT  - NK alloreactivity
OT  - acute lymphoblastic leukemia
OT  - acute myeloid leukemia
OT  - graft-vs-host disease
OT  - haploidentical hemopoietic stem cell transplantation
OT  - killer Ig-like receptors
OT  - natural killer cells
EDAT- 2013/02/05 06:00
MHDA- 2013/02/05 06:01
PMCR- 2013/01/01
CRDT- 2013/02/05 06:00
PHST- 2012/10/17 00:00 [received]
PHST- 2013/01/08 00:00 [accepted]
PHST- 2013/02/05 06:00 [entrez]
PHST- 2013/02/05 06:00 [pubmed]
PHST- 2013/02/05 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2013.00015 [doi]
PST - epublish
SO  - Front Immunol. 2013 Feb 1;4:15. doi: 10.3389/fimmu.2013.00015. eCollection 2013.