GLORIA

GEOMAR Library Ocean Research Information Access

Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
Filter
  • American Society of Hematology  (20)
Materialart
Verlag/Herausgeber
  • American Society of Hematology  (20)
Sprache
Erscheinungszeitraum
Fachgebiete(RVK)
  • 1
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 733-733
    Kurzfassung: Background: Little is known about the role of the CD56+ natural killer (NK) cell dose on the outcome of allogeneic peripheral blood stem cell transplantation (PBSCT). Recently, a higher dose of NK cells has been associated with a lower incidence of severe GVHD in a PBSCT setting. Therefore, the current study attempted to evaluate the effect of the NK cell dose on transplant outcomes, including non-relapse mortality (NRM) and infectious events, in an allogeneic PBSCT setting. Methods and Materials: Sixty-one cytokine mobilized PBSC recipients from HLA-matched sibling donors were analyzed according to the infused dose of CD34+ cells and NK cells in relation to overall survival (OS), NRM, GVHD, and infectious events. Results: The group of patients that received a higher dose of NK cells (≥ 5x107/Kg) showed a lower incidence of NRM (p=0.0186) and infectious events (p=0.0107). When confining the analysis to the group that received a CD34+ cell dose of ≥ 6x106/Kg, those patients that received a higher dose of NK cells exhibited a lower incidence of extensive chronic GVHD (p=0.0704). In a multivariate analysis using Cox’s regression model, a higher dose of NK cells was significantly associated with better transplant outcomes (for NRM, NK cell dose p=0.042, for CD34+ cell dose p=0.018; for infectious events, NK cell dose p=0.013, CD34+ cell dose 0.016; for bacterial infection, NK cell dose p=0.049). The group that received a higher NK cell dose also showed a faster immune recovery (p=0.046 for NK cell recovery, p=0.034 for helper T-cell recovery) in serial measurements of peripheral lymphocyte subsets at D+90, +180, and +365. Conclusions: The present data suggests that a high dose of NK cells may play an important role in improving transplant outcomes, in terms of reducing NRM and infectious events together with CD34+ cells. The protective role of NK cells against infections may also be associated with a faster immune recovery after allogeneic PBSCT. Figure Figure Figure Figure
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2004
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 2
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5202-5202
    Kurzfassung: Background: Detecting the variable number of tandem repeats (VNTRs) between the recipient and the donor has already been adopted to monitor the degree of chimerism after allogeneic stem cell transplantation (SCT). In allogeneic SCT, besides MHC-disparity, the disparity of various polymorphous proteins encoded by several genes may play a critical role in the pathogenesis of graft-versus-host disease (GVHD). However, the biologic effect of VNTR disparity has scarcely been studied. Materials & Methods: Eighty-four patients receiving an SCT from HLA-identical sibling (n=68) or unrelated donors (n=16) were analyzed. The enrolled diseases included AML 48, ALL 8, CML 15, NHL 10, and high-risk MDS 3. A PCR was performed to amplify 3 VNTR regions (D1S80, D1S111, and D17S5). The disparity was classified as fully matched, partially matched, or mismatched pairs. Results: A strong correlation was observed between the D1S80 disparity and the transplant outcomes in terms of OS (p=0.0179) and NRM (p=0.0305), yet not for the D1S111 or D17S5 disparity. The fully matched D1S80 pairs showed a better OS (72% vs 38%) and lower NRM (17% vs 50%) compared to the partially matched or mismatched pairs. In multivariate analyses, a fully matched D1S80 pair was found to be an independent favorable prognostic factor for OS (p=0.03) and NRM (p=0.05). In addition, D1S80 disparity was significantly associated with the occurrence of gut chronic GVHD (p=0.05). Conclusion: The present data suggest that disparities in D1S80 - located in chromosome 1 - seemed to be associated with an increased incidence of gut chronic GVHD and NRM. Figure. Overall survial (A) and non-relapse mortality (B) according to D1S80 VNTR disparity Figure. Overall survial (A) and non-relapse mortality (B) according to D1S80 VNTR disparity
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2005
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 3
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5201-5201
    Kurzfassung: Background: The current study attempted to evaluate the role of a simple quantitative measurement of peripheral lymphocyte subsets, especially CD4+ helper T-cell recovery, in predicting transplant outcomes, including overall survival (OS), non-relapse mortality (NRM), and opportunistic infections, after allogeneic stem cell transplantation (SCT). Methods: A total of 69 patients receiving an allogeneic SCT were included. The disease entities were as follows: AML 42, ALL 5, CML 15, NHL 5, and high-risk MDS 2. The peripheral lymphocyte subset counts, such as CD3+ T-cells, CD3+4+ helper T-cells, CD3+8+ cytotoxic T-cells, CD19+ B-cells, and CD56+ natural killer (NK) cells, were measured 3, 6, and 12 months post-transplant. Results: The CD19+ B-cell reconstitution was slow, while a rapid CD56+ NK cell recovery was noted. The CD4+ helper T-cell reconstitution at 3 months was strongly correlated with OS (p & lt;0.0001), NRM (p=0.0007), and opportunistic infections (p=0.0108) when stratifying patients with cut-off value of 200×106/L CD4+ helper T-cells. A rapid CD4+ helper T-cell recovery was also independently associated with a higher CD4+ helper T-cell transplant dose (p=0.006) and donor type (p & lt;0.001) in a regression analysis. An early CD4+ helper T-cell recovery at 3 months was associated with a subsequent faster helper T-cell recovery until 12 months, yet not with B-cell recovery. In a multivariate survival analysis, a combination of a higher CD34+ cell dose and rapid recovery of CD4+ helper T-cells at 3 months was found to a have favorable prognosis in terms of OS (p=0.001, hazard ratio [HR] 3.653) and NRM (p=0.005, HR 4.836), yet not relapse. Conclusion: A rapid recovery of the CD4+ helper T-cell count above 200×106/L at 3 months seemed to correlate with a faster immune reconstitution and predict a successful transplant outcome. Figure. The overall survival according to the helper T-cell counts at 3 months (A) and the difference of total T-(B) and helper T-cell (C) immune reconstitution within 1-year post-transplant according to helper T-cell counts at 3 months Figure. The overall survival according to the helper T-cell counts at 3 months (A) and the difference of total T-(B) and helper T-cell (C) immune reconstitution within 1-year post-transplant according to helper T-cell counts at 3 months
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2005
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 1757-1757
    Kurzfassung: Background: The pharmacokinetic impact of multidrug resistance-1 (MDR1) gene single nucleotide polymorphisms (SNPs) has been already investigated in solid organ transplantation field, however, data is still lacking in an allogeneic stem cell transplantation (SCT) setting. Methods: A total of 82 patients receiving an allogeneic HLA-identical sibling (n=70) or unrelated SCT (n=12) with graft-versus-host disease (GVHD) prophylaxis of cyclosporine-A (CSA) plus methotrexate (MTX) were included in the current study. Two SNPs of MDR1 gene (C3435T and G2677T/A) were analyzed using PCR/RFLP assay. Results: As regards G2677T/A SNP, GG genotype showed a higher incidence of NRM compared to non-GG genotype (67% vs. 32%, p=0.0073), yet not C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival (OS) was significantly correlated with G2677T/A genotype (p=0.0048), yet not with C3435T (p=0.5041) or MDR1 haplotype (p=0.4086). However, no difference in the relapse incidence was noted according to G2677T/A, C3435T genotype or MDR1 haplotype. In a multivariate analysis, those patients without GG genotype at G2677T/A were found to have favorable prognosis in terms of OS (p=0.003) or NRM (p=0.031) along with occurrence of chronic GVHD (p & lt;0.001 for OS, p=0.001 for NRM), standard disease risk (p=0.045 for OS) or acute grade 0,1 GVHD (p=0.019 for NRM). However, no correlation was found between the blood concentrations of CSA and MDR1 genotype and CSA neurotoxicity and MDR1 genotype. Conclusion: The G2677T/A genotype seemed to be associated with the transplantation outcomes, especially NRM. Further study is warranted to clarify its mechanism of MDR1 SNPs other than pharmacokinetic aspects. Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2005
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 5
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5479-5479
    Kurzfassung: The Durie-Salmon (DS) stage has been the gold standard for stratification of MM patients. However, the system does not contain beta-2 microglobulin (B2M) widely recognized as the single most powerful prognostic parameter. Recently, The Southwest Oncology Group (SWOG) staging system (Jacobson JL, et al. Br J Haematol122:441–50, 2003) and the International Staging System (ISS) (Greipp PR, et al. J Clin Oncol23:3412–20, 2005) utilizing B2M have been proposed. We aimed to evaluate whether the stage assessed at the time of ASCT by DS, SWOG, or ISS predict outcome following ASCT in patients with MM. Between November 1996 and December 2004, a total of 141 patients with MM who were treated with ASCT at 5 institutions in Korea were available for this analysis. The distribution of patients’ stage at ASCT by 3 staging systems was as Table 1. With a median follow-up of 20 months from ASCT, the median event-free survival (EFS) and overall survival (OS) were 16 months (95% confidence interval [CI], 11–21) and 56 months (95% CI, 38–74), respectively. The median survival of each stage group according to 3 staging systems at ASCT was as Table 2. Differences in EFS among the stage groups were not statistically significant. However, OS after ASCT was dependent on the SWOG stage at the time of ASCT and also significantly longer in patients with ISS stage I than others (NR vs. 39 months, P =.001). In this study, OS following ASCT was influenced by the stage according to SWOG or ISS, but not DS. The distribution of patients by 3 staging systems Stage I II III IV DS 32 (23%) 23 (16%) 86 (61%) - SWOG 53 (38%) 66 (47%) 16 (11%) 6 (4%) ISS 85 (60%) 34 (24%) 22 (16%) - Median event-free survial and overall survival by 3 staging systems Stage I II III IV P EFS=evnet-free survival, OS=overall survival, NR=not reached, * in months EFS* DS 27 17 13 - .40 SWOG 22 15 24 4 .21 ISS 17 13 10 - .63 OS* DS NR 58 40 - .17 SWOG NR 41 32 17 .045 ISS NR 32 40 - .0042
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2005
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 6
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 422-422
    Kurzfassung: Introduction: The current study attempted to evaluate the association between the IL-10 promoter gene polymorphism and transplant outcomes, including the occurrence of chronic GVHD and its clinical course during systemic immunosuppressive treatment (IST) after allogeneic peripheral blood stem cell transplantation (PBSCT). Methods: Three single-nucleotide polymorphisms in the proximal region of the IL-10 promoter gene (−1082/−819/−592) were analyzed in 60 recipients of cytokine-mobilized PBSCs from HLA-matched sibling donors, and the transplant outcomes compared in terms of the occurrence of chronic GVHD and its clinical course. Results: The current study only found two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC] ). An increased occurrence of chronic GVHD was noted dependent on the IL-10 haplotype (43% vs 68% vs 96% in ACC/ACC vs ATA/ACC vs ATA/ATA haplotype, p=0.003). In a logistic regression based on a multinomial model, the ATA/ATA homozygote presented a 7-fold increased risk of the development of chronic GVHD compared with the ACC/ACC homozygote. The cumulative incidence of chronic GVHD at 1 year post-transplant was 46±20%, 64±10%, and 82±5% in the ACC/ACC, ATA/ACC, and ATA/ATA groups, respectively (p=0.0266). The recipients without the ACC haplotype had a more frequent history of acute exacerbation of chronic GVHD (p=0.031, odds ratio 6.750), while 72% of the recipients with the ACC haloptype did not experience any history of acute exacerbation after the initiation of systemic IST for chronic GVHD compared to 38% of those without the ACC haplotype (p=0.014, odds ratio 4.375). Plus, the duration of systemic IST was significantly shorter in the recipients without the ATA-haplotype compared to those with the ATA haplotype (339 days versus 1,146 days, p=0.0091). In terms of GVHD-specific survival, the recipients without the ATA haplotype showed a 100% survival compared to 70.5% for the ATA haplotype group (p=0.2825). Conclusion: The IL-10 promoter gene polymorphism was found to be apparently associated with the occurrence of chronic GVHD and its clinical course during systemic IST for chronic GVHD in an allogeneic PBSCT setting. Figure Figure Figure Figure
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2004
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 7
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4889-4889
    Kurzfassung: Abstract 4889 Benzopyrenes are well known pollutants and carcinogens. They can intercalate into DNA and interfere transcriptions, resulting in causing various human diseases. However, biomarkers of benzopyrene toxicity have not been comprehensively studied in blood and leukemia cells. The current study was investigated to discover biomarkers for benzopyrene exposure in blood cells and leukemia cell lines. Peripheral blood, peripheral blood hematopoietic stem cell and leukemia cells (THP-1, K562, Molt-4 and HL-60) were cultured in RPMI 1640 media with adding 0, 50, 100 and 200μM of benzopyrene. Viability and apoptosis were assessed by tryptophan blue dye exclusion test and flowcytometry using annexin V. Hydrogen peroxide was measured using enzyme immunoassay. Mitochondrial mass, membrane potential and mitochondrial DNA (mtDNA) copy number were measured using MitoTracker Green, Red probes and real time PCR, respectively. The number of cell remained constant for three weeks culture. Viability of four cell lines disclosed significant decrease after two weeks of benzopyrene treatment. Apoptosis was increased in time- and dose-dependent manner after two weeks of benzopyrene treatment. Mitochondrial contents and membrane potentials were dramatically increased in three-week culture at dose dependent manner. Hydrogen peroxide level was significantly elevated after two weeks treatment of benzopyrene compared to non-benzopyrene treatment group. The number of mtDNA copy increased gradually after exposure to benzopyrene. These results indicated that increased mitochondrial mass and mtDNA copy number were biomarkers for direct exposure of benzopyrene in blood cells and hematopoietic tissues. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2011
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 8
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5365-5365
    Kurzfassung: Parathyroid hormone (PTH) is synthesized and secreted by the chief cells of the parathyroid gland. PTH has a positive impact on hematopoietic stem cells by indirectly decreasing hematopoietic cell apoptosis, and is currently being investigated as a potential therapeutic to stimulate hematopoiesis and enhance bone marrow engraftment. According to previous study, it was hypothesized that elevated PTH may mediate the induction of multiple myeloma (MM) through the biologic effects of IL-6. However, there was no comprehensive study regarding clinicopathological implications of PTH in MM. This study investigated the pathological and clinical implications of serum PTH in MM patients and relationship with other risk factors of MM. Patients and Methods A total of 115 patients who were newly diagnosed with MM were enrolled between 2006 and 2012. Serum PTH level was measured by automated 2-site chemiluminescent sandwich assay (Abbott Diagnostics). The medical parameters were reviewed for age, sex, PTH, plasma cell percentage in bone marrow, serum M protein, immunoglobulin level, free light chain (FLC) - kappa and lambda, FLC ratio, calcium, creatinine, hemoglobin, albumin, beta-2 microglobulin, lactate dehydrogenase (LDH), international staging system (ISS) stage, international myeloma working group (IMWG) response, chromosome abnormality, bone lesion, treatment outcome, and so on. The collected data was analyzed by PASW 18.0. We performed Spearman’s correlation analysis, Mann Whitney U-test, Kruskall Wallis test, time dependent Cox regression analysis, survival analysis by Kaplan-Meier method, etc. Results Serum PTH level of 115 myeloma patients was 24.7±34.9 (ranged 0.0-284.1) pg/mL. Serum level of IgG, IgM, FLC-lambda, albumin, and LDH was in positive correlation with serum PTH. Age, plasma cell percentage, M protein, IgA, FLC-kappa, FLC ratio, calcium, creatinine, hemoglobin, and beta-2 microglobulin showed negative correlation with PTH. Among those above, IgM (rho=0.190, p=0.045) and calcium (rho=-0.220, p=0.043) revealed statistically significant correlation with serum PTH. Serum PTH level in MM patients was not significantly different according to the group of IMWG response (p=0.450) and ISS stage (p=0.414). Meanwhile, there was no significant difference of PTH according to chromosomal abnormality (p=0.353), bone lesion (p=0.207), and disease progression (p=0.322). Besides, only calcium level was meaningfully different (p=0.016) by the comparison of clinical parameters between MM patient’s group with high PTH level and non-high PTH group (cut-off PTH level=68.3 pg/mL, Mann Whitney U-test). Relative to non-high PTH ( 〈 68.3 pg/mL) group, the hazard ratio was higher for group with high PTH level (≥68.3 pg/ml) ([HR] 3.037; p=0.524; 95% CI, 0.100∼92.586; Table 1). With regard to the prognostic implication of serum PTH value, the patient group with above 68.3 pg/mL showed moderate, inferior progression free survival (PFS) than non-high PTH group (median, 5 months vs. 13 months, p=0.056, Fig.1B). However, no overall survival (OS) differences were found between high PTH group and non-high PTH group (Fig. 1A). Interestingly, subgroup analysis showed that patients with high PTH level significantly had an inferior PFS than those with non-high PTH level. In detail, the subgroup were as follows; patients who reached the complete remission (CR) state (N=25) defined by IMWG response criteria at the end of follow up period (median, 3 months vs. 41 months, p=0.001, Fig.1C), patients (N=41) who belonged to ISS stage II (median, 1 months vs. 15 months, p=0.006, Fig.1D), patients (N=97) with no chromosome abnormality (median, 4 months vs. 15 months, p=0.034, Fig.1E), patients (N=28) who have undergone transplantation (median, 3 months vs. 18 months, p=0.009, Fig.1F). Conclusion This study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2013
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 9
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2802-2802
    Kurzfassung: Many reports state that hematopoietic malignancies mostly result from somatic mutations in HSCs in the bone marrow. Somatic mutations of spliceosomal gene such as SF3B1, U2AF1 and SRSF2 have been widely described in myelodysplastic syndrome (MDS). Some studies presented that MDS patient with splicing factor mutations influence the clinical outcomes. However, the clinical significances for the treatment of hypomethylating agents (HMA) in splicing factor mutation were not reported. Therefore, this study investigated the influences of the SF3B1, U2AF1 and SRSF2 splice gene mutation in MDS patients who received the HMAs. Materials and Methods MDS harboring ring sideroblast and association with somatic spliceosomal gene mutation was well demonstrated but, comparatively rare and showed good prognosis. So, we excluded MDS harboring ring sideroblast in this study. The study cohort of 133 MDS patients without harboring ring sideroblast was examined for somatic mutations in SF3B1, U2AF1 and SRSF2 splicing gene using direct sequencing method and 59 out of 133 patients received the treatment of HMAs (43 of Azacitidine and 16 of decitabine) for the treatment of MDS. Using the international prognostic scoring system(IPSS), the treatment indications for the HMA were as follows, 1) inermediate-1 with anemia and no response for the treatment of erythropoietin, 2) intermediate-1 with anemia accompanying other cytopenia ( neutrophil 〈 1,000/uL or PLT 〈 100,000/uL), 3) intermediate-2 or high risk. The response analysis was followed the modified IWG MDS response criteria. Results In 59 patients, mutations in K700E of SF3B1; S34T, S34P or Q157P of U2AF1; P95H or P95R of SRSF2 were found in 6 (10.2%), 7 (11.8%), and 4 (6.8%) patients, respectively. The 17 patients were observed any mutation (SF3B1, U2AF1 or SRSF2) in 59 patients. We compared the clinical features, treatment responses and survivals according to the somatic mutations of spliceosomal gene vs wild type (WT) in each mutation. The disease composition of 59 patients was like as follows; 1 of MDS with del(5q), 6 of RCUD, 24 of RCMD, 9 of RAEB-1, 19 of RAEB-2. In the clinical features, lower risk (according to IPSS, WPSS and revised-IPSS) patients was included in the group with SF3B1 mutation (P 〈 0.05). The hematologic improvement or more response for the HMA was observed in 33% vs 47% in SF3B1 mutation vs WT, 29% vs 48% in U2AF1 and 75% vs 44% in SRSF2, respectively. There was no difference in the response rates for the HMA therapy according to the mutation or wild type (P 〉 0.05). Overall survival did not show the statistical differences in each mutation (P 〉 0.05). The leukemia free survival in patients with SRSF2 mutation was inferior to the WT (p=0.001). However, anyone showed the leukemic transformation in the patients with SF3B1 mutation without statistical significance (p=0.247) (Fig. 1). Conclusion Our results show that mutation of SF3B1, U2AF1 and SRSF2 spliceosomal gene in MDS patients without harboring ring sideroblast did not influence the treatment response and overall survival for the HMAs. However, alteration of SRSF2 splice gene may be regarded as a risk factor of leukemic transformation. So, the patients with SRSF2 mutation treated with HMA have to consider the aggressive therapy such as allogeneic stem cell transplantation before leukemic transformation. To confirm this result, it will be needed more study for large number of patients. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2013
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 10
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1221-1221
    Kurzfassung: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that are potent mutagens and classified as carcinogens by International Agency for Research on Cancer. However, genotoxic effect of PAHs exposure has not been thoroughly presented in peripheral blood stem cells (PBSC) and bone marrow-mesenchymal stem cells (BM-MSC). Therefore, this study investigated the profiling of PAHs-induced genotoxicity in hematopoietic and mesenchymal stem cells using primary human-derived PBSC and BM-MSC. Zebrafish (Danio rerio) as in vivo vertebrate model was used for monitoring genotoxicity of PAHs exposure to the PBSC and BM-MSC. Materials and Methods Cytokine stimulation (10 mg/kg/d) was used in three healthy male donors from 5 d before to 2 d after. One to three apheresis procedures were planned for on day 0, day 1, and day 2, using a Baxter CS-3000 PLUS machine (Baxter Healthcare) and a COBE-Spectra (Gambro) for obtaining PBSC. Previous published protocol was used for the isolation and characterization of BM-MSCs. For in vitro cell line study, cells were cultured and maintained in RPMI media containing 10% fetal bovine serum and four types of PAHs- benzopyrene (BaP), pentacene, fluoranthene and pyrene - were added in the cell culture media with 100µM concentration. Cellular level of hydrogen peroxide as a representative marker of reactive oxygen species was measured using enzyme immunoassay. Mitochondrial mass, membrane potential and mitochondrial DNA (mtDNA) copy number were measured using MitoTracker Green, Red probes and real time PCR, respectively. Proteomics in mitochondrial-rich cytoplasmic fraction was performed using nano-LC-ESI-MS/MS analysis with the BioWorksBrowser (Thermo Fisher Scientific Inc., CA) and the SEQUEST search engines. For in vivo model study, Zebrafish embryos 30h post-fertilization (hpf) were exposed to BaP at concentrations of 200, 400, 600, 800 and 1000nM. Seventy embryos were cultured in 40 mL BaP solution in each petri dish, and there were three replicates for each of the five treatments. Embryos were collected at 54 hpf, 78hpf and 102hpf for the study of genotoxicity and morphological changes. Results According to each type of PAHs, the results of cell biology study showed different aspects: fluoranthene displayed profound significant reduction in cell count, especially in PBSC and viability decreased substantially after two days of exposuring into fluoranthene. On the third day of PAHs exposure, viability reduced remarkably in all the cells. Each type of cells displayed different proportionality of apoptosis. The proportion of apoptosis and cellular ROS level were increased in time- and dose-dependent manner after 3 days of PAHs treatment with different degree levels according to the type of PAHs. Mitochondrial contents and membrane potentials were increased with different pattern: mtDNA copy number and mass were dramatically elevated after 5-day treatment of fluoranthene and pyrene in both stem cells and in vivo Zebrafish model. Several hundreds of cellular proteins in mitochondrial-rich cytoplasmic fraction were profoundly deregulated in comparison to control group. The notable deregulated proteins for PAHs exposure were displayed as following: prelamin-A/C isoform 3 and annexin A1 for benzopyrene; prelamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly [ADP-ribose] polymerase 1 (PARP-1) for fluoranthene; talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, prelamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities in the general shape of Zebrafish, including curved backbone and cardiomegaly, were observed in the 54 hpf with more than 400 nM of BaP. Conclusion This study showed global profiling of toxic changes of PAHs in PBSC and BM-MSC as well as Zebrafish model. The change of mitochondrial genome (increased mtDNA copy number and mass) was closely associated with PAH exposure in hematopoietic and mesenchymal stem cells. Among cellular proteins, prelamin-A/C isoform 3, talin-1 and annexin A1 were remarkably elevated after exposure of PAHs, this may play a role as biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2013
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie hier...