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2.
Ann Hematol ; 103(5): 1775-1777, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38556531

RESUMEN

Pure red cell aplasia (PRCA) is a rare bone marrow (BM) disorder characterized by ineffective erythropoiesis, reduced reticulocyte count, normocytic anemia, and the absence of erythroid precursors. Here, we present a rare instance of PRCA occurring after ABO-matched allo-HSCT in a refractory/relapsed acute myeloid leukemia (R/R AML) patient. In this case, the patient received a combination treatment of Gilteritinib, Venetoclax, and Azacitidine. Remarkably, this treatment not only reduced myeloblasts but also facilitated the restoration of erythroid hematopoiesis.


Asunto(s)
Compuestos de Anilina , Enfermedades de la Médula Ósea , Compuestos Bicíclicos Heterocíclicos con Puentes , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Pirazinas , Aplasia Pura de Células Rojas , Sulfonamidas , Humanos , Azacitidina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Aplasia Pura de Células Rojas/etiología , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Enfermedades de la Médula Ósea/complicaciones
3.
Immun Ageing ; 21(1): 15, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378602

RESUMEN

BACKGROUND: With the development of Hematopoietic Stem Cell Transplantation (HSCT) technology, increasing numbers of elderly patients were undergoing allogeneic HSCT and elderly patients with hematologic malignancies could benefit most from it. Preformed donor-specific human leukocyte antigen (HLA) antibodies (DSA) were associated with graft failure in HLA-mismatched allogeneic HSCT and the absence of DSA was the main criterion of selecting the donor. Except for sensitization events such as transfusion, pregnancy or previous transplantation, ageing affects the humoral immune response both quantitatively and qualitatively. To evaluate the prevalence and distribution of anti-HLA and antibodies of MHC class I chain related antigens A (MICA) specificities in different age groups before initial HSCT would provide HLA and MICA specific antibody profiles under the impact of ageing, which could provide meaningful information in the process of selecting suitable HLA-mismatched donors by avoiding preformed DSA. RESULTS: There were no significant differences in the distribution of anti-HLA class I, class II and anti-MICA antibodies among the three age groups in this study except that a significant lower negative ratio of anti-HLA class I, class II antibodies and higher positive rate of MICA antibodies with maximum mean fluorescent intensity (MFI) > 5000 in the elderly than in young age group. The distribution of antibody specificities against HLA -A, -B, -C, -DR, -DQ, -DP and MICA antigens in the three age groups were generally consistent. The anti-HLA class I antibody specificities with higher frequencies were A80,A68;B76,B45;Cw17, which were unlikely to become DSA in Chinese. Anti-HLA class II antibody specificities were more likely to become potential DSA than class I.DR7, DR9, DQ7, DQ8 and DQ9 were most likely to become potential DSA. CONCLUSIONS: The prevalence of anti-HLA and anti-MICA antibodies increased slightly as age increased. While ageing had a small impact on the distribution of antibody specificity frequencies against HLA-A, -B, -C, -DR,-DQ, -DP and MICA antigens in recipients awaiting initial HSCT from East China. The risk of developing preformed DSA was basically consistent in the three age groups and the elderly group might be more favorable in HLA-mismatched HSCT due to higher positive rate of anti-MICA antibody.

4.
J Glob Antimicrob Resist ; 31: 279-285, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36265801

RESUMEN

OBJECTIVES: Refractory cytomegalovirus reactivation (RCR) after allo-hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes. Current studies for the risk factors and survival of patients with post-transplantation RCR remain limited. METHODS: 163 patients with Cytomegalovirus (CMV) reactivation undergoing allo-HSCT in Jiangsu Province hospital from Jan 2013 to Dec 2020 were analyzed retrospectively. RESULTS: Multivariate analysis revealed that highest CMV viremia>1 × 104copies/mL (hazard ratio [HR] 16.895, 95% confidence interval [CI] 3.394-84.109, P = 0.001) and platelet count at Day 90 of more than 87.3 × 109/L (HR 0.381, 95% CI 0.154-0.945, P = 0.037) were independent risk factors affecting RCR. As for prognosis of patients with CMV reactivation, results showed that patients with RCR had higher risk of non-relapse mortality (NRM) (39.5% vs. 22.5%, P = 0.045), and RCR was an independent risk factor for NRM (HR 2.216, 95% CI 1.137-4.317, P = 0.019). There was no significance between patients with or without RCR in terms of overall survival (OS) (50.7% vs. 55.6%, P = 0.281) and relapse-free survival (RFS) (43.6% vs. 52.0%, P = 0.179). The landmark analysis showed that patients with RCR had higher NRM (P = 0.01), worse OS (P = 0.02), and RFS (P =0.01) within 100 days after transplantation. Patients with hemorrhagic cystitis (40.9% vs. 64.5%, P =0.028) and who developed viremia>1 × 105copies/mL (43.4% vs. 58.4%, P = 0.033) were associated with worse OS. CONCLUSION: Factors such as higher viral load, thrombocytopenia, and ATG used in conditioning therapy increased the incidence of RCR. Patients with RCR had worse NRM, OS, and RFS within 100 days after transplantation.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Humanos , Citomegalovirus/fisiología , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Viremia/etiología , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Factores de Riesgo , Recurrencia
6.
Hematology ; 26(1): 295-300, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33648437

RESUMEN

OBJECTIVE: To investigate the impact of minimal residual disease (MRD) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of acute leukemia. METHODS: Data from 114 patients who were diagnosed with acute leukemia (AL) and underwent allo-HSCT between Jan 2013 and Dec 2019 were collected and analyzed. The patients were attributed into MRD positive (MRD+) group and MRD negative (MRD-) group. RESULTS: Among the 114 acute leukemia patients, there were 32 MRD+ patients before transplantation, and 82 MRD- patients. No significant difference was found between the MRD+ group and the MRD- group in the incidence of acute graft-versus-host disease (aGvHD) (p = 0.09). Compared with the MRD+ group, the MRD- group had a higher incidence of chronic graft-versus-host disease (cGvHD) (p = 0.008). There is no significance in relapse between the two groups (p = 0.084), while the incidence of relapse was seemingly higher in the MRD+ group: 36.9% Vs 19.7% . We attributed to the lack of sample size and NRM in MRD+ group was remarkably higher. The MRD+ group had significantly worse one-year overall survival (OS) ( , p = 0.003) and one-year progression-free survival (PFS) (, p = 0.009). In the multivariate analysis, MRD+ was an independent prognostic factor for OS (HR = 1.898; 95%CI 1.042-3.457; p = 0.036). CONCLUSION: Pre-transplantation MRD positive status is a risk factor for survival and prognosis after HSCT. Upon this, emphasis should be put on (1) screening more efficient chemo regimen with targeted agents, to help patients reach and keep MRD- status before transplantation; (2) designing better management with different GvHD prophylaxis treatment, timely disease monitoring and preemptive intervention on relapse.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Neoplasia Residual/terapia , Adolescente , Adulto , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Pronóstico , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto Joven
7.
World J Clin Cases ; 9(3): 614-622, 2021 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-33553399

RESUMEN

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is widely used in the treatment of hematological diseases. However, complications after transplantation, such as acute and chronic graft-vs-host disease (GVHD), still seriously affect the quality of life and even threaten the lives of patients. There is evidence that glomerular diseases can manifest as GVHD. However, GVHD should not occur as a result of syngeneic HSCT. CASE SUMMARY: A 20-year-old male diagnosed with T lymphoblastic lymphoma (stage IIIA, aaIPI 1) in September 2013 was treated with six cycles of hyper-CVAD and achieved complete remission. He underwent syngeneic HSCT in June 2014, and had no kidney disease history before the transplant. However, nephrotic syndrome occurred 24 mo later in the patient after syngeneic HSCT. Renal biopsy was performed, which led to a diagnosis of atypical membranous nephropathy. After treatment with glucocorticoids combined with cyclophosphamide and cyclosporine, the nephrotic syndrome was completely relieved. CONCLUSION: We report a case of delayed nephrotic syndrome after syngeneic HSCT. Antibody-mediated autoimmune glomerular disease may be the underlying mechanism. After treatment with immunosuppressive agents, the nephrotic syndrome was completely relieved but further long-term follow-up is still needed.

8.
Hematol Oncol ; 37(4): 392-400, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31420873

RESUMEN

Ibrutinib, a first-generation Bruton's tyrosine kinase (BTK) inhibitor, could improve immunity of relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients. Whether zanubrutinib, a second-generation selective BTK inhibitor, has similar effects as ibrutinib remains to be determined. Dynamics of number and immunophenotype of immune cells during zanubrutinib treatment in 25 R/R CLL/SLL patients were examined by flow cytometry and blood routine tests. The expression intensity of programmed death-1 (PD-1) on total CD4+ (P < .01), total CD8+ (P < .01), and T helper cells (P < .05) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on total CD4+ (P = .010) and regulatory T cells (P < .05) reduced after treatment. There were significant differences in expression intensity of CD19 (P < .01), C-X-C chemokine receptor type 5 (CXCR5) (P < .01), and CD49d (P < .05) on B cells before and after treatment. Downregulation of PD-1 on T cells and CXCR5 and CD19 on B cells were observed in nearly all patients after zanubrutinib treatment. Programmed death-ligand 1 expression downregulated, especially in the female, CLL, normal spleen, normal ß2-macroglobulin (ß2-MG) and abnormal lactate dehydrogenase (LDH) subgroups, and CTLA-4 expression on CD4+ T cells tended to decrease in the male, old, CLL, splenomegaly, abnormal ß2-MG, normal LDH, IGHV-mutated and wild-type tumor protein 53 subgroups after zanubrutinib treatment. These findings suggest that zanubrutinib can regulate immunity primarily by improving T cell exhaustion, inhibiting suppressor cells and disrupting CLL cells migration through downregulation of adhesion/homing receptors. Furthermore, favorable changes in cell number and immunophenotype were preferably observed in patients without adverse prognostic factors.


Asunto(s)
Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Proteínas de Neoplasias/antagonistas & inhibidores , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Antineoplásicos/farmacología , Subgrupos de Linfocitos B/efectos de los fármacos , Femenino , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunofenotipificación , Células Asesinas Naturales/efectos de los fármacos , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Piperidinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Receptores de Antígenos de Linfocitos B/inmunología , Subgrupos de Linfocitos T/efectos de los fármacos
11.
Biomed Pharmacother ; 95: 743-748, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28888211

RESUMEN

OBJECTIVE: To illustrate the association of MDR1 (Multidrug Resistance 1) polymorphisms at loci 1236, 2677, 3435 and the prognosis of multiple myeloma (MM) in Jiangsu population. METHODS: A total of 129 MM patients were recruited from Jiangsu Province, China. The DNA was extracted from white blood cells (WBC) of peripheral blood and was amplified by polymerase chain reaction-allele specific primers (PCR-ASP). MDR1 polymorphisms at 3 loci were analyzed by electrophoresis followed by photograph or DNA direct sequencing. The association between the MDR1 and clinical outcomes were calculated by Graphpad and SPSS. RESULTS: MDR1 alleles at locus C1236T with T had significant lower calcium level in MM patients compared with C. The genotype CT had a significantly prolonged progress free survival (PFS) compared genotype CC at locus C1236T (median time: 48 months vs. 28 months, respectively; p=0.0062; HR=0.21; 95%CI0.061-0.715) while patients carrying T allele (CT and TT) at locus C3435T had a longer PFS than patients without T allele (CC) (median time: 60 months vs. 29 months, respectively; p=0.038; HR=0.508; 95%CI 0.264-0.978). And a borderline significance was found in haplotype at loci 2677-3435 and PFS. No significant findings were revealed between OS and MDR1 polymorphisms. CONCLUSION: MDR1 polymorphisms could affect the prognosis of multiple myeloma whereas more samples and a longer follow-up are also needed.


Asunto(s)
Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Haplotipos/genética , Mieloma Múltiple/genética , Polimorfismo de Nucleótido Simple/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Alelos , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia
12.
Curr Stem Cell Res Ther ; 12(1): 14-18, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27396370

RESUMEN

Since the improvement of chemotherapy and innovation of rituximab, about 60% of patients with diffuse large B cell lymphoma (DLBCL) could receive long-term survival after firstline therapy. Around 30% fail to respond or experience relapse considered as the relapsed/refractory DLBCL, the highdose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) has been used as the second-line treatment. However, the patients relapse after auto-HSCT or not eligible for the auto-HSCT have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the potentially curative way in such kind of patients. In this paper, we collected the published data about patients with relapsed/refractory DLBCL who underwent allo-HSCT, demonstrated the appropriate candidate for allo-HSCT, identified the effect of the donor types on the recipients, presented the major conditioning regimens for allo-HSCT and figured out the outcomes of each conditioning regimen. We also tried to identify the prognostic factors on the outcome which might shed some light on the further clinical application.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Recurrencia Local de Neoplasia/terapia , Rituximab/uso terapéutico , Terapia Recuperativa/métodos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Humanos , Prednisona/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Insuficiencia del Tratamiento , Vincristina/uso terapéutico
13.
Leuk Res ; 50: 72-77, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27693855

RESUMEN

OBJECTIVES: Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis. METHODS: TIGAR mRNA expression was investigated by quantitative PCR in 102 newly diagnosed CLL patients. Furthermore, the relationship between the expression of TIGAR and its clinical characteristics and prognosis were investigated. Moreover, we also investigated the correlation between TIGAR expression and apoptosis in primary CLL cells. RESULTS: Our data revealed that TIGAR overexpression was correlated with the protection from spontaneous apoptosis in CLL cells, and is strongly associated with advanced Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 positivity, ß2-microglobulin and p53 aberrations. Higher expression of TIGAR was associated with shorter treatment-free survival (median: three months vs. 51 months, P=0.0108), worse overall survival (median: 74 months vs. not reached, P=0.0242), and the diverse responses to fludarabine-based chemotherapy. TIGAR expression in patients resistant to chemotherapy was significantly higher than in patients sensitive to chemotherapy (mean: 0.3859±0.1710 vs. 0.0974±0.0291, P=0.0290). CONCLUSION: Taken together, our findings revealed that high TIGAR expression is closely correlated with worse clinical outcome in CLL patients, and depicted how bioenergetic characteristics could be therapeutically exploited in CLL.


Asunto(s)
Proteínas Reguladoras de la Apoptosis , Apoptosis , Glucólisis , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Adulto , Anciano , Supervivencia Celular , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Monoéster Fosfórico Hidrolasas , Pronóstico , ARN Mensajero/análisis , Análisis de Supervivencia , Resultado del Tratamiento , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/fisiología , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Adulto Joven
14.
Zhonghua Xue Ye Xue Za Zhi ; 37(4): 308-12, 2016 Apr.
Artículo en Chino | MEDLINE | ID: mdl-27093994

RESUMEN

OBJECTIVE: To investigate the effectiveness and safety of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC allo-HSCT) in ultra high risk chronic lymphocytic leukemia (CLL) patients with the deletion of p53 to deepen the understanding of allo-HSCT in the treatment of CLL. METHODS: In this retrospective study, a total of 4 ultra high risk CLL patients with the deletion of p53 in our center between July 2012 and Jan 2014 were enrolled. The RIC regimen was administered and the hematopoietic reconstitution, transplantation related mortality (TRM), overall survival (OS), progress free survival (PFS) were evaluated. RESULTS: We registered 4 patients with the median age of 56 years (49-61 years), including 3 males and 1 female. The median mononuclear cells (MNC) and CD34(+) cells were 6.54 (2.85-14.7) × 10(8)/kg (recipient body weight) and 5.81 (2.85-7.79) × 10(6)/kg (recipient body weight), respectively. The median time of the neutrophil recovery was 11 days (range of 9-12 days), and the median time of the platelet recovery 5.5 days (range of 0-11 days). Three patients (75%) attained a full donor chimerism at day 28 after transplantation and one (25%) got a mixed chimerism of donor and recipient. During the follow-up at a median time of 26.5 months (range of 21-39 months), 2 (50%) patients developed acute graft versus host disease (aGVHD) grade I and 2 (50%) patients got CMV infection. One patient got herpes zoster virus and EB virus infections. No transplantation related mortality was found in the 4 patients. One patient who was in partial response status progressed 5 months after transplantation, and the other 3 patients remained in durable remission after allo-HSCT. CONCLUSION: These results suggested that RIC allo-HSCT showed durable remission, good tolerance and acceptable toxicity, which could be a better option for the treatment of ultra high risk CLL patients with the deletion of p53 and was worth to be investigated and applied widely in future.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Crónica de Células B/terapia , Acondicionamiento Pretrasplante , Proteína p53 Supresora de Tumor/genética , Supervivencia sin Enfermedad , Femenino , Eliminación de Gen , Genes p53 , Enfermedad Injerto contra Huésped , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
15.
Oncotarget ; 7(16): 21631-43, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-26950276

RESUMEN

Aberrant activation of lymphoid enhancer-binding factor-1 (LEF1) has been identified in several cancers, including chronic lymphocytic leukemia (CLL). As a key transcription factor of the Wnt/ß-catenin pathway, LEF1 helps to regulate important genes involved in tumor cell death mechanisms. In this study, we determined LEF1 gene expression levels in CLL (n = 197) and monoclonal B-cell lymphocytosis (MBL) (n = 6) patients through real-time RT-PCR. LEF1 was significantly up-regulated in both MBL and CLL patients compared with normal B cells. Treatment-free survival (TFS) time and overall survival (OS) time were much longer in CLL patients with low LEF1 expression than in those with high LEF1 levels. Furthermore, Wnt inhibitor ethacrynic acid (EA) induced both apoptosis and necroptosis in primary CLL cells. EA also enhanced the cytotoxicity of both fludarabine and cyclophosphamide against CLL cells in vitro. Finally, we demonstrated that EA functions by inhibiting the recruitment of LEF1 to DNA promoters and restoring cylindromatosis (CYLD) expression in CLL cells. Our results showed, for the first time, that high LEF1 expression is associated with poor survival for CLL patients. Combined with other chemotherapeutic drugs, EA may be a promising therapeutic agent for CLL.


Asunto(s)
Apoptosis/efectos de los fármacos , Ácido Etacrínico/farmacología , Regulación Leucémica de la Expresión Génica , Leucemia Linfocítica Crónica de Células B/genética , Factor de Unión 1 al Potenciador Linfoide/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Enzima Desubiquitinante CYLD/genética , Enzima Desubiquitinante CYLD/metabolismo , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/metabolismo , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Masculino , Persona de Mediana Edad , Necrosis/genética , Necrosis/prevención & control , Pronóstico , Interferencia de ARN , Análisis de Supervivencia , Células Tumorales Cultivadas , Adulto Joven
16.
Tumour Biol ; 37(7): 9549-54, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26790444

RESUMEN

Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein (P-gp), which acts as an efflux pump and provides cell protection against various substances, and its single-nucleotide polymorphisms (SNPs) are associated with the development of malignant hematologic diseases. The present study aimed at investigating whether the MDR1 SNPs and haplotype variants were correlated with the susceptibility to multiple myeloma (MM). A total of 115 MM patients and 153 healthy controls from Jiangsu Han population were enrolled and genotyped by polymerase chain reaction-allele-specific primer (PCR-ASP) method or DNA direct sequencing at MDR1 loci of C1236T, G2677T/A, and C3435T. No significance was found in the distribution of alleles and genotypes in MDR1 three loci. Diplotype analysis has also demonstrated no effect in susceptibility to MM. But, in haplotype analysis, the haplotype of T-G-T was significantly more common than healthy controls (12.6 % in MM group vs. 1.7 % in control group, odds ratios (ORs) = 8.7, 95 % confidence interval (CI) 3.3-22.8, Pc < 0.01). Our results pointed out that comparable allele, genotype, and diplotype frequencies among MM patients and controls in Chinese Jiangsu Han population were found; the frequency of T-G-T haplotype was significantly increased in MM group compared with the control group, which indicated that this haplotype might be associated with the susceptibility to MM.


Asunto(s)
Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Haplotipos/genética , Polimorfismo de Nucleótido Simple/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Alelos , Femenino , Frecuencia de los Genes/genética , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética
17.
Tumour Biol ; 37(1): 1237-44, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26286835

RESUMEN

MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 ± 12.6 vs. 57.7 ± 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Polimorfismo de Nucleótido Simple , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anciano , Alelos , Pueblo Asiatico , China , Supervivencia sin Enfermedad , Femenino , Genotipo , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/etnología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Modelos de Riesgos Proporcionales , Inducción de Remisión
18.
Int J Clin Exp Pathol ; 8(6): 7588-93, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26261674

RESUMEN

Aplastic anemia (AA) patients with prolonged immunosuppression have a risk of development of lymphoproliferative disorders (LPDs), especially combined with Epstein-Barr virus (EBV) infection. However, development of nature killer/T (NK/T) cell lymphoma, in a nontransplantation setting, has not been documented for AA patients with immunosuppressive therapy (IST). Herein, we described a middle-aged man, Han ethnic, who presented with swelled parotid gland after a long history of IST for AA. Fever, night sweating, weight loss had not been found. Increased heterotypic lymphocytes had been detected in the left side of parotid gland demonstrated as cCD3(+), CD56(+), GranB(+), TIA-1(+), MUM-1(+), KI-67 (50%-75%)(++), Bcl-6(-), MPO(-) by immunohistochemistry, and in-situ hybridization (ISH) indicated EBER positive. Chromosome analysis by R banding method revealed 46, XY [20]. NK/T cell lymphoma concurrent with aplastic anemia was diagnosed and a mild chemotherapy regimen including vincristine, prednisone, L-asparaginase was administered. The parotid mass was gradually regressed after the first cycle of chemotherapy. The patient discharged from the hospital voluntarily and lost the follow-up.


Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/patogenicidad , Inmunosupresores/efectos adversos , Linfoma Extranodal de Células NK-T/virología , Adulto , Anemia Aplásica/diagnóstico , Anemia Aplásica/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Examen de la Médula Ósea , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Humanos , Huésped Inmunocomprometido , Inmunohistoquímica , Hibridación in Situ , Linfoma Extranodal de Células NK-T/química , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/inmunología , Masculino , ARN Viral/genética , Resultado del Tratamiento
19.
Biomed Pharmacother ; 73: 24-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26211578

RESUMEN

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR=1.48, 95% CI: 1.08-2.02, Pc=0.03; GT: OR=1.96, 95% CI: 1.25-3.07, Pc<0.01), while genotype AT in this locus seemed to be protective (OR=0.29, 95% CI: 0.02-0.72, Pc=0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR=2.38, 95% CI: 1.52-3.74, Pc<0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR=5.21, 95% CI: 2.58-10.54, Pc<0.01); haplotype of G-T in 2677-3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR=3.97, 95% CI: 2.31-6.85, Pc<0.01; 2677GT/3435TT: OR=4.55, 95% CI: 2.02-10.22, Pc<0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677-3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.


Asunto(s)
Pueblo Asiatico/genética , Haplotipos/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Polimorfismo de Nucleótido Simple/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Oncotarget ; 6(21): 18374-88, 2015 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-26158410

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Patients with DLBCL harboring MYC aberrations concurrent with BCL2 or/and BCL6 aberrations constitute a specific group with extremely poor outcome. In this study, we retrospectively investigated the incidence and prognosis of MYC, BCL2, and BCL6 aberrations with DLBCL patients in Chinese population. We applied fluorescence in situ hybridization and immunohistochemical analysis in 246 DLBCL patients. The results showed that patients with MYC or BCL2 copy number aberration (CNA) had significantly worse overall survival (OS) and progression-free survival (PFS) than negative cases (P < 0.0001). Patients with both MYC and BCL2 CNA had similar outcomes to those with classic double hit lymphoma or protein double expression lymphoma (MYC and BCL2/BCL6 coexpression). By multivariate analysis, MYC CNA, BCL2 CNA and double CNA were the independent worse prognostic factors. In conclusions, patients with MYC or BCL2 CNA constituted a unique group with extremely poor outcome and may require more aggressive treatment regimens.


Asunto(s)
Variaciones en el Número de Copia de ADN , Predisposición Genética a la Enfermedad/genética , Linfoma de Células B Grandes Difuso/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Adulto , Pueblo Asiatico/genética , China/epidemiología , Supervivencia sin Enfermedad , Femenino , Predisposición Genética a la Enfermedad/etnología , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Incidencia , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/etnología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Estudios Retrospectivos
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