KIR repertory in patients with hematopoietic diseases and healthy family members

AbstractBackgroundSince the discovery of specific histocompatibility, literature has associated genes involved in the immune response, like the Human Leucocyte Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA genes may also influence the immune process, such as the genes encoding the immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented in HLA class I molecules that are genetically polymorphic, also observed in KIR genes, led to the investigation of the relevance of the KIR system to hematopoietic stem cell transplant. The cure of patients with leukemias and other hematological malignancies after bone marrow transplantation (BMT) has been attributed in part to the ability of the donor immune cells, present in the graft, to recognize and eliminate neoplastic cells of the patient. The cytotoxic activity of NK cells is mediated by the absence of HLA class I-specific ligands on the target cell surface to inhibitory KIR receptors (hypothesis of “missing-self”).MethodsWe analyzed, by PCR typing-SSOP technique, the presence or absence of 16 KIR genes and haplotypes of 39 patients with hematopoietic disorders and 136 healthy individuals from Paran á State. The comparisons made between the patient and control group were performed using χ2 test or Fisher exact test (bilateralp-value), as appropriated. Significance level was...
Source: BMC Hematology - Category: Hematology Source Type: research

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Conclusions The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion This case demonstrates successful cure of pre-B-ALL complicating XLA by alloSCT with restoration of B-cell development and functional antibody response. We are aware of only one previous case of pre-B-ALL in an XLA patient (21), which suggests that human BTK deficiency in itself does not predispose to pre-B-ALL. However, there are data to suggest that BTK may act as a tumor suppressor, and BTK deficiency may predispose to tumor development following a “second hit.” Mice with a genetic deficiency in Slp65, a gene encoding an adaptor protein that functions together with BTK, have a block in progenito...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: This prospective multicenter study provides information on the current incidence and outcome of IFD in the real life setting. Practice variation between the centers may help to ultimately improve antifungal management in children at highest risk for IFDs. Introduction Available data on the incidence and outcome of invasive fungal diseases (IFD) in children treated for a hematological malignancy or undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are mostly based on single site, retrospective studies or on studies performed prior to the availability of newer compounds such as broad-sp...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion:More than half of the patients with acute leukemia had CRE colonization of the gut at the time of presentation. Chemotherapy interruptions and deaths during induction were seen in a significantly higher number of patients colonized with CRE at the time of presentation. Patients with acute leukemia should be screened for CRE colonization of the gut prior to induction chemotherapy. This assumes importance is centres with high prevalence of CRE colonization as CRE colonisation of the gut is a predictor for induction mortality.References:J. de Naurois, I. Novitzky-Basso, M.J. Gill etal, Management of febrile neutrop...
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Poster III Source Type: research
Introduction:Allogeneic hematopoietic cell transplantation (alloHCT) has historically been reserved for younger, fit patients with hematologic malignancies. With the introduction of non-myeloablative conditioning regimens and improved supportive care, alloHCT has been increasingly offered to older adults.Objectives:To determine the association between functional status as measured by a cancer-specific comprehensive geriatric assessment (CGA) and post-transplant outcomes in an older alloHCT patient population.Methods:We conducted a prospective cohort study of patients aged 50 or older who underwent alloHCT at the University...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Poster II Source Type: research
DiscussionHaploidentical transplantation with PTCy is a feasible therapeutic option in pediatric patients with malignant hematological diseases who require a HSCT and do not have a matched sibling or unrelated donor available.Conflict-of-interest disclosure: The authors declare they have nothing to disclose.Correspondence: Gerardo López-Hernández. loherge@gmail.comBibliographyKlein OR, Buddenbaum J, Tucker N, et al. Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies. Biol Blood Marrow ...
Source: Blood - Category: Hematology Authors: Tags: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities Source Type: research
In conclusion, as none of the pretransplant characteristics were found to influence the ability to select the patients that will benefit from HSC transplantation, this work supports offering HSCT to all active leukaemia eligible patients with reasonable performance status. Copyright © 2016 John Wiley &Sons, Ltd.
Source: Hematological Oncology - Category: Hematology Authors: Tags: Original Research Article Source Type: research
Abstract Older recipient and donor age were associated with higher incidences of severe graft‐versus‐host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome a...
Source: American Journal of Hematology - Category: Hematology Authors: Tags: Research Article Source Type: research
Conditions:   Adult Acute Lymphoblastic Leukemia in Remission;   Adult Acute Myeloid Leukemia in Remission;   Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities;   Adult Acute Myeloid Leukemia With Del(5q);   Adult Acute Myeloid Leukemia With Inv(16)(p13;q22);   Adult Acute Myeloid Leukemia With t(15;17)(q22;q12);   Adult Acute Myeloid Leukemia With t(16;16)(p13;q22);   Adult Acute Myeloid Leukemia With t(8;21)(q22;q22);   Adult Nasal Type Extranodal NK/T-cell Lymphoma; &...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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