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1.
HLA ; 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681275

RESUMO

The importance of anti-HLA antibodies in transplantation settings, such as HLA-mismatched or haploidentical hematopoietic stem cell transplantation and platelet refractoriness, is widely recognized. In previous reports, it was mentioned that several cut-off values of donor-specific anti-HLA antibodies mean fluorescence intensity (MFI) were related to graft rejection in the environment of HLA mismatched stem cell transplantation and the aim of this study was to investigate the prevalence and risk factors of anti-HLA antibodies according to those cut-off values of MFI. A total of 3805 patients with hematologic disease were prospectively enrolled and analyzed. When using MFI of anti-HLA antibodies ≥500, ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000 as cut-off values for positivity, the prevalence of class I or II anti-HLA antibodies ranged from 4.6% to 20.2% in all cases. When the MFI cut-off value was ≥500 for positivity, multivariate analysis indicated that platelet transfusion, underlying disease, and pregnancy were the most important risk factors for the presence of anti-HLA antibodies for the total patients. Subgroup analysis according to age, gender, and underlying disease showed that pregnancy was the most important risk factor for the presence of anti-HLA antibodies. For all patients (n = 3805), when anti-HLA antibody positivity was defined according to different MFI cut-off values, including ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000, an association of platelet transfusion and pregnancy with anti-HLA antibodies was also demonstrated. Our results suggest that pregnancy and platelet transfusion are the main risk factors for the prevalence of anti-HLA antibodies in haploid allograft candidates, providing evidence for guiding the evaluation of anti-HLA antibodies and helping donor selection for HLA-mismatched transplant candidates.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35735203

RESUMO

BACKGROUND: ZNF384 rearrangement has been recently identified as a new subtype of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive studies clarifying immunophenotypic features and discriminating them from non-ZNF384 in adult BCP-ALL remain scarce to date. METHODS: Flow cytometric assessments were retrospectively performed in 43 patients with ZNF384 rearrangement, 45 with BCR-ABL1, 29 with KMT2A rearrangement and 44 with other BCP-ALL in the analysis cohort. RESULTS: CD33- and CD13-positive frequencies were significantly higher in patients with ZNF384 rearrangement than in those with non-ZNF384; however, no significant difference was observed in CD10- and CD123-positive frequencies. Analysis of antigen-positive cell proportion and median fluorescence intensity (MFI) further indicated that patients with ZNF384 rearrangement had significantly lower CD10 and higher CD33, CD13, and CD123 proportion and MFI. However, compared with KMT2A rearrangement, the CD10 expression in patients with ZNF384 rearrangement was higher, with the median percentage and MFI of 36.16 (3.63-94.79)% versus 4.53 (0.03-21.00)%, and 4.50 (0.86-32.26) versus 2.06 (0.87-4.04), respectively (p < 0.0001). Furthermore, compared with BCR-ABL1 and other BCP-ALL, ZNF384 rearrangement had significantly higher CD33 and CD13 proportion and MFI (p < 0.0001 and p < 0.05, respectively). In addition, higher CD123 proportion and MFI in ZNF384 rearrangement than those in the other three groups were reported for the first time (p < 0.01). A flow cytometry scoring system, including CD10%, CD33MFI, CD13%, and CD123MFI, was proposed and verified to predict ZNF384 rearrangement with high sensitivity and specificity, that is, 76.74% and 91.53% in the analysis and 87.50% and 91.30% in the validation cohort. CONCLUSIONS: The multiparameter immunophenotypic scoring system could suggest ZNF384 rearrangement.

4.
Environ Technol ; : 1-14, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35481789

RESUMO

Salix psammophila wood flour /polyvinyl alcohol hydrogel composite membrane (SPPM) with high adsorption capacity and good cycle adsorption performance was prepared by wet spinning technology. The SPPM was characterised by the scanning electron microscope (SEM), specific surface area test (BET), energy dispersive spectrum (EDS) thermal gravimetric analysis (TGA), fourier transform infrared spectroscopy (FT-IR), and x-ray photoelectron spectroscopy (XPS). The results showed that the surface of SPPM is rough and porous, with good pore structure and thermal stability, and mercury ions (Hg(II)) have been successfully adsorbed on SPPM. At the same time, the effects of adsorption conditions (Hg(II) initial concentration, pH, adsorption time, and temperature) on the adsorption performance of SPPM were studied. Results from the adsorption experiment showed that the adsorption capacity of SPPM for Hg(II) can reach 426 mg/g. After four adsorption and desorption experiments, the adsorption capacity can reach 375 mg/g, which indicates that SPPM has good cycle adsorption performance. The adsorption kinetics was better described by the Pseudo-second-order kinetic, and their adsorption isotherms were fitted for the Langmuir model. The obtained results showed that SPPM is an available, economical adsorbent and was found suitable for removing Hg(II) from an aqueous solution.

6.
Pediatr Hematol Oncol ; 39(2): 97-107, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34156313

RESUMO

Abnormally high ecotropic viral integration site 1 (EVI1) expression has been recognized as a poor prognostic factor in acute myeloid leukemia patients. However, its prognostic impact in B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unknown. A total of 176 pediatric Ph-negative BCP-ALL patients who received at least 1 course of chemotherapy and received chemotherapy only during follow-up were retrospectively tested for EVI1 transcript levels by real-time quantitative PCR at diagnosis, and survival analysis was performed. Clinical and EVI1 expression data of 129 pediatric BCP-ALL patients were downloaded from therapeutically applicable research to generate effective treatments (TARGET) database for validation. In our cohort, the median EVI1 transcript level was 0.33% (range, 0.0068-136.2%), and 0.10% was determined to be the optimal cutoff value for patient grouping by receiver operating characteristic curve analysis. Low EVI1 expression (<0.10%) was significantly related to lower 5-year relapse-free survival (RFS) and overall survival (OS) rates (P = 0.017 and 0.018, respectively). Multivariate analysis showed that EVI1 expression <0.10% was an independent adverse prognostic factor for RFS and OS. TARGET data showed that low EVI1 expression tended to be related to a lower 5-year OS rate (P = 0.066). In conclusion, low EVI1 expression at diagnosis could predict poor outcomes in pediatric Ph-negative BCP-ALL patients receiving chemotherapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1939818 .


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
7.
Leuk Lymphoma ; 63(1): 152-161, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34405769

RESUMO

Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease and needs to be stratified. Both, cancer cells and immune cells participate in tumor initiation, growth and progression and might affect clinical outcomes. TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3), an immune checkpoint molecule, is expressed not only on immune cells but also on leukemic stem cells (LSCs) in AML. This prompted us to investigate the prognostic significance of TIM-3 in t(8;21) AML. A total of 47 t(8;21) AML patients were tested for TIM-3 expression by multi-parameter flow cytometry at diagnosis. 35 of these, who received chemotherapy alone or along with allogeneic hematopoietic stem cell transplantation were followed up. The expression pattern of TIM-3 on T-cells and NK (natural killer) cells as a whole (T + NK) and LSCs were evaluated independently. High percentage of T + NK - TIM-3+ and CD34+CD38-TIM-3+ cells were significantly associated with a high 2-year cumulative incidence of relapse (CIR) (p = 0.028, 0.016). Further, concurrent high frequencies of T + NK-TIM-3+ and CD34+CD38-TIM-3+ cells at diagnosis were significantly associated with a high 2-year CIR (p < 0.0001) and this together with c-KIT D816 mutation were the independent adverse prognostic factors for relapse (hazard ratio (HR)=2.5, [95% confidence interval (CI), 1.1-6.0], p = 0.04; HR = 46.5, [95% CI, 2.7-811.5], p = 0.009). In conclusion, the expression pattern of TIM-3 on both T and NK cells and LSCs at diagnosis had prognostic significance in t (8;21) AML.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A , Leucemia Mieloide Aguda , Antígenos CD34/metabolismo , Citometria de Fluxo , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/uso terapêutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Células-Tronco Neoplásicas/metabolismo , Prognóstico
8.
Curr Med Sci ; 41(3): 443-453, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34185250

RESUMO

We performed a retrospective analysis to investigate dynamic peri-hematopoietic stem cell transplantation (HSCT) minimal/measurable residual disease (MRD) on outcomes in patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 271 patients were enrolled and classified into three groups: unchanged negative MRD pre- and post-HSCT group (group A), post-MRD non-increase group (group B), and post-MRD increase group (group C). The patients in group B and group C experienced a higher cumulative incidence of relapse (CIR) (42% vs. 71% vs. 16%, P<0.001) and lower leukemia-free survival (LFS) (46% vs. 21% vs. 70%, P<0.001) and overall survival (OS) (50% vs. 28% vs. 72%, P<0.001) than in group A, but there was no significant difference in non-relapse mortality (NRM) among three groups (14% vs. 12% vs. 8%, P=0.752). Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR (HR=2.392, 95% CI, 1.816-3.151, P<0.001), LFS (HR=1.964, 95% CI, 1.546-2.496, P<0.001) and OS (HR=1.731, 95% CI, 1.348-2.222, P<0.001). We also established a risk scoring system based on dynamic peri-HSCT MRD combined with remission status pre-HSCT and onset of chronic graft-versus-host disease (GVHD). This risk scoring system could better distinguish CIR (c=0.730) than that for pre-HSCT MRD (c=0.562), post-HSCT MRD (c=0.616) and pre- and post-MRD dynamics (c=0.648). Our results confirm the outcome predictive value of dynamic peri-HSCT MRD either alone or in combination with other variables for patients with T-ALL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Recidiva , Linfócitos T/patologia , Adulto Jovem
9.
J Phys Chem Lett ; 12(23): 5534-5539, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34100612

RESUMO

The electronic angular momentum projected onto the diatomic axis couples with the angular momentum of the nuclei, significantly affecting the rotational motion of the system under electronic excitations by intense lasers. In this letter, we propose a pump-probe photodissociation scheme for an accurate determination of electron-rotation coupling effects induced by the strong fields. As a showcase we study the CH+ molecule excited by a short intense ultraviolet pump pulse to the A1Π state, which triggers coupled rovibrational dynamics. The dynamics is observed by measuring the kinetic energy release and angular resolved photofragmentation upon photodissociation induced by the time-delayed probe pulse populating the C1Σ+ state. Simulations of the rovibrational dynamics unravel clear fingerprints of the electron-rotation coupling effects that can be observed experimentally. The proposed pump-probe scheme opens new possibilities for the study of ultrafast dynamics following valence electronic transitions with current laser technology, and possible applications are also discussed.

11.
Front Oncol ; 11: 632532, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816270

RESUMO

Novel recurrent fusion gene types such as zinc finger protein 384 (ZNF384) fusions have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with the application of next-generation sequencing technologies. However, the comprehensive large-scale clinical cohort study for clarifying their prognostic significance remains scarce to date. A total of 242 consecutive adult Ph-negative BCP-ALL patients treated in our institute were retrospectively screened ZNF384 fusions at diagnosis by multiplex real time quantitative PCR. ZNF384 fusions were identified in 47 patients (19.4%) and all belonged to B-other ALL (having no high hyperdiploid karyotype, BCR-ABL1, TCF3-PBX1, ETV6-RUNX1, or MLL rearrangement). In the whole cohort, patients with ZNF384 fusions had significantly higher 3-year relapse-free-survival (RFS) and tended to have a higher 3-year overall survival (OS) than those with no ZNF384 fusions (80.1% vs. 52.5%, P = 0.013; 67.6% vs. 54.0%, P = 0.10). For patients receiving chemotherapy alone and received allogeneic-hematologic stem cell transplantation (allo-HSCT) were censored at the time of transplantation, patients with ZNF384 fusions had both similar RFS and similar OS to B-other ALL patients with no ZNF384 fusions (RFS: P =0.94 and 0.30; OS: P =0.94 and 0.51). For patients receiving transplantation, those with ZNF384 fusions had significantly higher 3-year RFS than B-other ALL patients with no ZNF384 fusions and their OS were similar (P = 0.022 and 0.24). Only two of 31 patients with ZNF384 fusions and receiving allo-HSCT relapsed, individually occurred 66.8 and 69.8 months after transplantation. Therefore, ZNF384 fusion is common in adult BCP-ALL, which may define a new group from BCP-ALL containing no classical fusion transcript with better prognosis through receiving allo-HSCT.

12.
Chin Med J (Engl) ; 134(10): 1199-1208, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33734137

RESUMO

BACKGROUND: For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. METHODS: A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. RESULTS: All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score. CONCLUSION: This new risk score system might stratify patients with different risks of relapse, which could guide treatment.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfócitos B , Humanos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante de Células-Tronco
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 43-48, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554795

RESUMO

OBJECTIVE: To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH+) propitiation to the relapse of t(8;21) acute myeloid leukemia(AML) patients before and after treatment. METHODS: Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed. RESULTS: All the patients were followed up for a median of 32 (2-52) months. The median percentage of CD34+CD38- and CD34+CD38-ALDH+ cells among nucleated cells were 2.7 (0.36-35.7)% and 0.017 (0.0013-0.62)% at diagnosis, respectively. Among the bone marrow samples in patients achieved CR, the median percentage of CD34+CD38- cells was 0.035 (0.0064-0.66)%, and it was significantly decreased as compared with the percentage at diagnosis (P<0.001); The median percentage of CD34+CD38-ALDH+ cells was 0.014 (0.0019-0.24)%, and it showed no different as compared with the percentage at diagnosis (P=0.45). Survival analysis showed that patients with higher percentage of CD34+CD38- and CD34+CD38-ALDH+ cells at diagnosis tended to the lower 3-year relapse-free survival (RFS) (P=0.27 and 0.21). Furthermore, patients with higher percentage of CD34+CD38- and CD34+CD38-ALDH+ cells when achieved CR had a significant lower 3-year RFS rates (P=0.010 and 0.0044) as compared with those with lower percentage of CD34+CD38- and CD34+CD38-ALDH+ cells. Multivariate analysis showed that higher percentage of CD34+CD38-ALDH+ cells when achieved CR was an independent factor affecting RFS of the patients. CONCLUSION: The percentage of CD34+CD38-ALDH+ cells at CR in t(8;21) AML patients could predicts relapse, and had more profound predictive significance for relapse than the percentage of CD34+CD38- cells.


Assuntos
Leucemia Mieloide Aguda , ADP-Ribosil Ciclase 1 , Antígenos CD34 , Citometria de Fluxo , Humanos , Células-Tronco Neoplásicas , Prognóstico , Recidiva , Indução de Remissão
14.
Leuk Lymphoma ; 62(1): 185-193, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902355

RESUMO

Acute myeloid leukemia with intermediate cytogenetic risk (ICR-AML) needs to be stratified and abnormal gene expression might be prognostic. PR/SET domain 16 (PRDM16) transcript levels were assessed in 267 consecutive adult ICR-AML patients at diagnosis by real-time quantitative PCR. 38.2% patients had PRDM16 transcript levels higher than the upper limit of normal bone marrow samples. Through ROC curve analysis and comparison of relapse-free survival (RFS), the optimal cutoff value of PRDM16 transcript levels was identified to group patients into high expression (PRDM16-H, 21.3%) and low expression (PRDM16-L). PRDM16-H was significantly associated with lower 4-year RFS and overall survival (OS) rates in the entire cohort, patients with normal karyotypes, FLT3-ITD (-) and NPM1 mutation (+)/FLT3-ITD (-) patients (all p < .05). Multivariate analysis showed that PRDM16-H was an independent adverse prognostic factor for RFS and OS in the entire cohort. Therefore, high PRDM16 expression at diagnosis predicts poor outcomes in adult ICR-AML patients.


Assuntos
Leucemia Mieloide Aguda , Adulto , China , Estudos de Coortes , Análise Citogenética , Proteínas de Ligação a DNA/genética , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico , Fatores de Transcrição/genética , Tirosina Quinase 3 Semelhante a fms
15.
Hematology ; 26(1): 9-15, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33357137

RESUMO

OBJECTIVES: Ras-related dexamethasone-induced 1 (RASD1) is abnormally expressed in many solid cancers. However, its potential role in adults with B-cell acute lymphoblastic leukemia (B-ALL) is unclear. Therefore, we aim to clarify the abnormal expression of the tumor-associated biomarker, RASD1, as a potential target for diagnosis and prognosis in adult Philadelphia-negative B-ALL. METHODS: The expression of RASD1 was detected with RT-qPCR in 92 adults with de novo Ph-negative B-ALL and 40 healthy controls. The correlation between RASD1 transcript levels and relapse was assessed. RESULTS: RASD1 transcript levels in patients with Ph-negative B-ALL (median 81.76%, range 0.22%-1824.52%) were significantly higher than those in healthy controls (7.59%, 0.46%-38.66%; P<0.0001). Patients with low RASD1 transcript levels had a lower 5-year relapse-free survival (RFS, 47.5% [32.9%, 62.1%] vs. 63.1% [49.0%, 77.2%]; P = 0.012) and a higher 5-year cumulative incidence of relapse (CIR, 52.0% [37.4%, 66.6%] vs. 36.2% [22.2%, 50.2%]; P = 0.013) especially in patients receiving chemotherapy only. Multivariate analysis showed that a low RASD1 transcript level was an independent risk factor for RFS (HR = 2.938 [1.427, 6.047], P = 0.003) and CIR (HR = 3.367 [1.668, 6.796], P = 0.001) in patients with Ph-negative B-ALL. CONCLUSIONS: RASD1 transcript levels were significantly higher in patients with Ph-negative B-ALL and a low RASD1 transcript level was independently correlated with increased relapse risk.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas ras/genética , Adolescente , Adulto , Idoso , Linfócitos B/patologia , Biomarcadores Tumorais/genética , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Regulação para Cima , Adulto Jovem
16.
Onco Targets Ther ; 13: 7545-7553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801773

RESUMO

PURPOSE: The cancer-testis antigen, which is a preferentially expressed antigen of melanoma (PRAME), is an ideal target for immunotherapy and cancer vaccines. Since the expression of this antigen is relevant to therapy responses, the heterogeneity in its expression and the underlying mechanism need to be investigated. PATIENTS AND METHODS: Plasma cell sorting was performed in 48 newly diagnosed multiple myeloma (MM) patients. Real-time quantitative PCR was performed to examine the PRAME transcript levels and gene copy numbers. Bisulfate clone sequencing of the PRAME promoter and exon 1b regions was performed in 4 patients. Quantitative methylation-specific PCR of the +287 CpG site was performed for all patients. The human MM cell lines RPMI8226, LP-1 and MOLP-2 were treated with 5-azacytidine. RESULTS: The median PRAME transcript level was 3.1% (range: 0-298.3%) in the plasma cells sorted from the 48 MM patients. Eleven (22.9%) and 37 (77.1%) patients were individually categorized into the PRAME low- and high-expression groups according to the cut-off value of 0.05%. The methylation ratios of the promoter and the 3' region of exon 1b region were both negatively related to the transcript levels. The degrees of methylation at the +287 CpG site were significantly negatively related to the transcript levels in all 48 patients (r=-0.44, P=0.0018), and those in the high-expression group (r=-0.69, P<0.0001) but not those in the low-expression group (r=-0.27, P=0.43). All 5 patients with homozygous deletions were categorized into the low-expression group. There were no significant differences in the PRAME transcript levels between the hemizygous deletion (n=8) and no deletion (n=35) groups (P=0.40). Furthermore, the PRAME transcript levels significantly increased in the MM cell lines after treatment with 5-azacytidine. CONCLUSION: Both methylation and copy number variation may participate in the regulation of PRAME expression in MM; in patients with no homozygous deletion, PRAME expression is mainly controlled by methylation, and a proportion of fairly low expression is caused by homozygous deletion.

17.
Front Oncol ; 10: 320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32257948

RESUMO

Background: This study compared the effects of pre-transplantation measurable residual disease (pre-MRD) on outcomes in Philadelphia chromosome (Ph)-positive ALL patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical SCT (haplo-SCT). Methods: A retrospective study (n = 202) was performed. MRD was detected by RT-PCR and multiparameter flow cytometry. Results: In the total patient group, patients with positive pre-MRD had a higher 4-year cumulative incidence of relapse (CIR) than that in patients with negative pre-MRD (26.1% vs. 12.1%, P = 0.009); however, the cumulative incidence of non-relapse mortality (NRM) (7.4% vs. 15.9%, P = 0.148), probability of leukemia-free survival (LFS) (66.3% vs. 71.4%, P = 0.480), and overall survival (OS) (68.8% vs. 76.5%, P = 0.322) were comparable. In the MSDT group, patients with positive pre-MRD had increased 4-year CIR (56.4% vs. 13.8%, P < 0.001) and decreased 4-year LFS (35.9% vs. 71.0%, P = 0.024) and OS (35.9% vs. 77.6%, P = 0.011) compared with those with negative pre-MRD. In haplo-SCT settings, the 4-year CIR (14.8% vs. 10.7%, P = 0.297), NRM (7.3% vs. 16.3%, P = 0.187) and the 4-year probability of OS (77.7% vs. 72.3%, P = 0.804) and LFS (80.5% vs. 75.7%, P = 0.660) were comparable between pre-MRD positive and negative groups. In subgroup patients with positive pre-MRD, haplo-SCT had a lower 4-year CIR (14.8% vs. 56.4%, P = 0.021) and a higher 4-year LFS (77.7% vs. 35.9%, P = 0.036) and OS (80.5% vs. 35.9%, P = 0.027) than those of MSDT. Multivariate analysis showed that haplo-SCT was associated with lower CIR (HR, 0.288; P = 0.031), superior LFS (HR, 0.283; P = 0.019) and OS (HR, 0.252; P = 0.013) in cases with a positive pre-MRD subgroup. Conclusions: Our results indicate that the effects of positive pre-MRD on the outcomes of patients with Ph-positive ALL are different according to transplant modality. For Ph-positive cases with positive pre-MRD, haplo-SCT might have strong graft-vs.-leukemia (GVL) effects.

18.
J Hematol Oncol ; 13(1): 27, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228710

RESUMO

BACKGROUND: Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal candidates warrants further investigation. METHODS: We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual disease (MRD) pre-transplantation who underwent HIDT (n = 169) or MSDT (n = 39). RESULTS: The cumulative incidence of positive MRD post-transplantation was 26% (95% CI, 19-33%) and 44% (95% CI, 28-60%) for HIDT and MSDT, respectively (P = 0.043). Compared to the HIDT cohort, the MSDT cohort had a higher 3-year cumulative incidence of relapse (CIR; 47%, 95% CI, 31-63% vs. 23%, 95% CI, 17-29%; P = 0.006) and lower 3-year probability of leukemia-free survival (LFS; 43%, 95% CI, 27-59% vs. 65%, 95% CI, 58-72%; P = 0.023) and overall survival (OS; 46%, 95% CI, 30-62% vs. 68%, 95% CI, 61-75%; P = 0.039), without a difference in non-relapse-mortality (10%, 95% CI, 1-19% vs. 11%, 95% CI, 6-16%; P = 0.845). Multivariate analysis showed that HIDT is associated with a low CIR (HR = 0.364; 95% CI, 0.202-0.655; P = 0.001) and better LFS (HR = 0.414; 95% CI, 0.246-0.695; P = 0.001) and OS (HR = 0.380; 95% CI, 0.220-0.656; P = 0.001). CONCLUSIONS: HIDT is better than MSDT in view of favorable anti-leukemia activity for patients with pre-transplantation MRD positive ALL. The current study paves the way to determine that haploidentical donors are the preferred choice regardless of available matched sibling donors in a subgroup population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02185261. Registered July 9, 2014. https://clinicaltrials.gov/ct2/show/NCT02185261?term=NCT02185261&draw=2&rank=1.


Assuntos
Seleção do Doador , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco , Transplante Haploidêntico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos Prospectivos , Irmãos , Transplante de Células-Tronco/métodos , Doadores de Tecidos , Transplante Haploidêntico/métodos , Adulto Jovem
19.
Eur J Haematol ; 105(2): 185-195, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32282962

RESUMO

BACKGROUND: Currently, the prognostic stratification and therapeutic evaluation systems for multiple myeloma (MM) lack specific molecular indicators. OC-STAMP is a new gene and is also highly expressed in MM. METHODS: A total of 160 MM patients have been investigated with both quantitative reverse transcription PCR (RT-qPCR), flow cytometry (FCM) and cytogenetic FISH on the same mononuclear cells isolated from bone marrow specimens. RESULTS: We found that OC-STAMP mRNA levels were significantly higher in newly diagnosed cases of MM than in healthy donors (median, 0.52% vs. 0.02%, P < .001). Moreover, the changes in the OC-STAMP mRNA levels paralleled the disease stages and minimal residual disease, as detected by FCM. Furthermore, we found that patients with high OC-STAMP mRNA levels were more likely to develop ≥3 bone lesions, be diagnosed with Durie-Salmon stages III, and have the P53 (17p13) deletion. In addition, advanced stage patients with high OC-STAMP mRNA levels had a lower 4-year progression-free survival (5.6% vs. 22.9%, P = .0055) and a worse 4-year overall survival (25.8% vs. 48.8%, P = .0137) compared to patients with low mRNA levels of this indicator. CONCLUSIONS: OC-STAMP may be a promising molecular indicator to monitor treatment effects and participate in the prognostic stratification of MM.


Assuntos
Biomarcadores Tumorais , Proteínas de Membrana/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea/patologia , Linhagem Celular Tumoral , Aberrações Cromossômicas , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Imunofenotipagem , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Análise de Sobrevida , Translocação Genética , Proteína Supressora de Tumor p53/genética
20.
Br J Haematol ; 190(2): 274-283, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32103499

RESUMO

About 25% of patients with newly diagnosed acute myeloid leukaemia (AML) have normal cytogenetics and no nucleophosmin 1 (NPM1) mutation or Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). The prognosis and best therapy for these patients is controversial. We evaluated 158 newly diagnosed adults with this genotype who achieved histological complete remission within two cycles of induction therapy and were assigned to two post-remission strategies with and without an allotransplant. Targeted regional sequencing at diagnosis was performed and data were used to estimate their prognosis, including relapse and survival. In multivariable analyses, having wild-type or mono-allelic mutated CCAAT/enhancer-binding protein alpha (CEBPA) [hazard ratio (HR) 2·39, 95% confidence interval (CI) 1·08-5·30; P = 0·032), mutated NRAS (HR 2·67, 95% CI 1·36-5·25; P = 0·004), mutated colony-stimulating factor 3 receptor (CSF3R) (HR 2·85, 95% CI 1·12-7·27; P = 0·028) and a positive measurable residual disease (MRD)-test after the second consolidation cycle (HR 2·88, 95% CI 1·32-6·30; P = 0·008) were independently correlated with higher cumulative incidence of relapse (CIR). These variables were also significantly associated with worse survival (HR 3·02, 95% CI 1·17-7·78, P = 0·022; HR 3·62, 95% CI 1·51-8·68, P = 0·004; HR 3·14, 95% CI 1·06-9·31, P = 0·039; HR 4·03, 95% CI 1·64-9·89, P = 0·002; respectively). Patients with ≥1 of these adverse-risk variables benefitted from a transplant, whereas the others did not. In conclusion, we identified variables associated with CIR and survival in patients with AML and normal cytogenetics without a NPM1 mutation or FLT3-ITD.


Assuntos
Análise Citogenética/métodos , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Sequências de Repetição em Tandem , Adulto Jovem
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