Natural killer (NK) cells are important immune cells in human body, which occupy an important place in adoptive immunotherapy for patients with malignancies due to their capacity of killing tumor cells without MHC limitation, as well as separating graft versus leukemia (GVL) and graft versus host disease (GVHD). Recent studies showed that different kinds of NK cell-surface receptors have been found, which transmit inhibiting signals or activating signals, the balance between them determines the functional status of NK cells. Researchers have focused on the study of NK cell-surface receptors recently in order to improve application of NK cells for adoptive immunotherapy. This review summaries the current advancement about NK cell-surface receptors and their clinical significance.
Animals ; Humans ; Immunotherapy, Adoptive ; Killer Cells, Natural ; Receptors, Natural Killer Cell

In treating of leukemia and controlling of minimal-residual disease (MRD), graft versus leukemia effect (GVL) plays a critical role, and complicated mechanisms are involved in this immunology process. When graft cells are infused into recipients, the evoked GVL effect must be inevitably influenced by many factors derived from allogeneic effect between donor and receptor. To utilize GVL more efficiently in future clinical practice and to improve the curative effect of allo-HSCT, it is necessary to recognize these factors. Some potential factors influencing GVL such as chimerism patterns, autocytotoxic cells, dynamics of immune cells in patients, the cytokines and so on are reviewed in this article.
Graft vs Leukemia Effect ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; immunology ; surgery

Objective To study the different expressions of receptor activator of nuclear factor-kappa B ligang(RANKL) mRNA in spleens of rats fed with diet of low calcium and high fluoride. Methods A 2× 2×2 factorial design was used and the factors were calcium, fluoride and action time. In the design, 40 Wistar rats [average body mass(118.9±13.5)g] were divided into four groups randomly by weight: control with normal diet (0.790%, calcium), low calcium group with low calcium intake(0.063%, calcium), high fluoride group with normal diet and high fluoride intake(100 mg/L, fluoride) and low calcium and high fluoride group with low calcium and high fluoride intake. After 4 and 8 months, 5 rats of each group were sacrificed and total RNA was extracted from spleen. And the expression levels of RANKL mRNA were determined by reverse transcription polymerase chain reaction (RT-PCR). Results At time of 4 months, the expression level of RANKL mRNA was 0.13± 0.05,0.13± 0.03,0.17±0.02,0.27± 0.05 and at time of 8 months, it was 0.11 ± 0.01,0.16 ± 0.02,0.16± 0.03,0.36 ± 0.07 in control group, low calcium group, high fluoride group, low calcium with high fluoride group, repectively. The factorial design AVONA showed that low calcium and high fluoride had significant effects on RANKL mRNA expression(F = 40.224,56.679, all P < 0.05) while action time had not(F = 2.850, P > 0.05 ). The interactions of low calcium with high fluoride or high fluoride with action time were signifieant(F = 7.247, 18.789, all P < 0.05) while the interaction of high fluoride with action time was not(F = 1.751, P > 0.05). Conclusions Low calcium alone or high fluoride alone or low calcium with high fluoride or low calcium with action time can increase the the RANKL mRNA expression level. High fluoride does not affect the RANKL mRNA level as the action time is prolonged.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine, its roles in the physiology and pathology of immune system, have been investigated thoroughly, great deal of data have been documented on its immunoregulatory activity. In this review, according to advance of study on HGF in recent years, the role of HGF in the immune regulation, such as immunoregulatory effects of HGF on T lymphocytes, B lymphocytes and dendritic cell, modulation of HGF on specific humoral and cellular immune response, control of acute GVHD and acceleration of myeloid and immunologic reconstitution in allogenetic bone marrow transplantation models, promotion of tissue repair and regeneration, and alleviation of immune rejection in allogeneic organ transplantation including the heart, liver and kidney transplantation, prevention of grafts from injury as well as applicably useful of HGF in the therapy of autoimmune disorders were summarized.
Animals ; Graft Rejection ; immunology ; prevention & control ; Graft vs Host Disease ; immunology ; prevention & control ; Graft vs Leukemia Effect ; immunology ; Hepatocyte Growth Factor ; physiology ; Humans ; Immunity, Cellular ; immunology

Objective To screen mutations in genes including ASXL1, TET2, IDH1, IDH2, SETBP1, MPL515, JAK2 exon 12 and JAK2V617 in 135 polycythemia vera (PV) patients. To assess progreasson and genomics characteristics post polycythemic myelofibrosis. Methods DNA sequencing of ASXL1(Exon12),TET2 (Exons 3-11),IDH1(Exon4),IDH2(Ex-on4),SEPBP1(Exon4),JAK2 exon 12 and MPL515 (Exon 10) genes were carried out using Sanger method. JAK2V617 muta-tion was detected by allele-specific PCR in patients with PV. In the mean time, the mutation load of JAK2V617F allele (V617F%) was evaluated by real-time PCR using Tagman MGB probe. Then, the significant of gene mutations and clinical outcomes of post-PV Myelofibrosis(PPMF)was analyzed. To study risk factors of PPMF, logistic regression were employed. Results ASXL1, TET2, IDH1, IDH2 were mutated in 7.69%(8/104), 5.26%(1/19) , 0.08%(1/120) and 0.08%(1/121) of all PV patient respectively. JAK2 was mutated in 82.22%(111/135) of PV patients with mutation rate of exon12 of 2.96%(4/135) and there were no mutation of MPL515 and SETBP1 in PV patients. ASXL1 mutation was found in 31.82%(7/22) PPMF patients. Spearman analysis showed that ASXL1 is correlated with JAK2V617F (V617F%) (rs=0.298,P=0.002). The hemo-globin was lower in patients with ASXL1 mutation than patient without mutation (wild type). Leukocyte count, V617F%>50%rate, thrombosis and PPMF were higher in patients with ASXL1 mutation than that of ASXL1 wild type(P＜0.05). ASXL1 mu-tation, V617F%>50% rate and splenomegaly were all risk factors of PPMF. Conclusion ASXL1 mutation is the risk-fac-tor of PPMF and may promote V617F%by some mechanism.

OBJECTIVETo analyze the kinetics of hematopoietic cell chimerism in the early period after non-myeloablative stem cell transplantation (NAST) and to investigate the correlation between molecular and hematologic assessment of engraftment or rejection.

METHODShort tandem repeat-polymerase chain reaction (STR-PCR) analysis of chimerism status was carried out in 6 patients who received NAST from HLA-matched sibling donors.

RESULTSIn 5/6 patients, the peripheral blood samples collected on the first day after allograft infusion displayed the presence of mixed chimerism. STR-PCR analysis revealed a gradual increase of the donor-specific allelic signal which became dominant over the recipient-specific allele by day +7. On day +14, hematologic chimerisms were completely donor origin. Their molecular engraftments (ME) were detected at a median time of 6 days, preceding hematologic engraftment by a median of 5 days (P > 0.05). But the sixth patient showed more than 50% host residual cells on day +7 and had no signs of ME on day +14.

CONCLUSIONIt suggested that molecular monitoring of the early dynamics of chimerism after NAST could be useful in predicting engraftment, or rejection. If the engraftment was less than 50% on day +7 and failed to get ME on day +14, the graft rejection would occur.

Adult ; Graft Rejection ; Graft vs Host Disease ; diagnosis ; etiology ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Kinetics ; Middle Aged ; Polymerase Chain Reaction ; Tandem Repeat Sequences ; Transplantation Chimera ; Transplantation, Homologous

OBJECTIVETo observe the therapeutic effect and major complications of haploidentical nonmyeloablative allogeneic peripheral blood stem cell transplantation (NST) for refractory or relapsed leukemia.

METHODSThe results of 30 patients, including 14 cases of acute myeloid leukemia (AML), 11 cases of acute lymphoblastic leukemia (ALL), 5 case of chronic myelogenous leukemia (CML) (accelerated and blastic phase) with refractory or relapsed leukemia (RF/RL) who underwent haploidentical NST from August 2000 to April 2009 were analyzed. The conditioning regimen consisted of fludarabine (flu), antithymocyte globulin (ATG), cyclophosphamide (CTX), total body irradiation (TBI) and cytarabine (Ara-C) or myleran (Bu). Graft-versus-host disease (GVHD) prevention programmes consisted of Cyclosporine (CsA), mycophenolate mofetil (MMF), CD25 monoclonal antibody combined with mesenchymal stem cells (MSC).

RESULTSTwenty six cases of patients were full donor engraftment and 4 cases mixed chimerism into full donor chimerism. The average duration of neutrophil >0.5×10⁸/L after NST was 11 (9-16) days, and platelet >20×10⁸/L 17 (12-60) days. Upon follow-up of 16 to 120 months, 12-month transplant-related mortality (TRM) was 46.7%, acute Ⅱ-Ⅳgraft-versus-host disease (aGVHD) incidence was 40.0%. The probability of 3-year disease relapse, EFS and overall survival (OS) rates were 16.7%, 46.2% and 50.0% respectively.

CONCLUSIONHaploidentical NST could improve OS and EFS of refractory or relapsed leukemia and reducce TRM to some extent.

Adolescent ; Adult ; Child ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia ; therapy ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

To explore the mechanism of CSA in the reversal of drug-resistance of leukemia cells, K562 and K562/ADM cells were used for in vitro study. Drug sensitivity of cells was evaluated by MTT assay and cell survival by trypan blue exclusion. Apoptosis was detected by terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL) and agarose gel electrophoresis. The results showed that 1.0 mg/L CSA alone have no effect on the survival of K562 and K562/ADM cell lines, but it could enhance the chemotherapy sensitivity of the 2 cell lines, and accelerate the apoptosis induced by ADM. These effects were stronger in K562/ADM cell line, when the concentration of CSA > 1.0 mg/L, CSA itself could kill leukemia cells and induce the apoptosis of the 2 cell lines. It is concluded that CSA can reverse leukemia cells' drug-resistance by enhance apoptosis of the leukemic cells, CSA itself can induce leukemia cells' apoptosis and kill leukemia cell too.

OBJECTIVETo study the changes of peripheral plasmacytoid dendritic cells and lymphocyte subsets in patients with chronic hepatitis B (CHB) during consensus interferon (CIFN) treatment.

METHODSTwenty-three patients with CHB were treated with CIFN for 24 weeks and followed up for another 24 weeks. Peripheral plasmacytoid dendritic cells and lymphocyte subsets were measured throughout the treatment and follow-up periods.

RESULTSAfter CIFN treatment, 43.5% of the patients had virological and biochemical responses. The percentage and absolute number of peripheral plasmacytoid dendritic cells decreased significantly (P less than 0.05), the number of CD3+ cells, CD4+ T cells, B cells and the ratio of CD4+/CD8+ cells decreased also (P less than 0.05), but the number of CD8+ T cells and NK cells increased (P less than 0.05).

CONCLUSIONSConsistent virological and biochemical responses can be seen in some patients with CHB virus infection after CIFN treatment, and the percentage and number of their peripheral plasmacytoid dendritic cells greatly decreased, but the number of CD8+ T cells and NK cells increased.

Adult ; Antiviral Agents ; therapeutic use ; CD8-Positive T-Lymphocytes ; immunology ; Dendritic Cells ; immunology ; Female ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Interferon-alpha ; therapeutic use ; Killer Cells, Natural ; immunology ; Male ; Young Adult

To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Coagulation ; Blood Coagulation Tests ; Child ; Female ; Fibrin Fibrinogen Degradation Products ; Hemorrhage ; pathology ; Humans ; Leukemia ; blood ; pathology ; Leukocyte Count ; Male ; Middle Aged ; Platelet Count ; Prothrombin Time ; Retrospective Studies ; Thrombin Time ; Young Adult