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1.
Br J Haematol ; 205(2): 634-644, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38924031

RESUMEN

In this study, we investigated whether matched and mismatched multidrug resistance gene (MDR1) genotypes (G2677TA, C1236T and C3435T) were associated with prognosis in patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). One hundred patients after transplantation and their donors were enrolled. Matched MDR1 G2677TA donor-recipient was associated with an increased risk of non-relapse mortality (NRM) (29.5% vs. 6.2%, p = 0.002), poor overall survival (OS) (51.7% vs. 63.8%, p = 0.024) and disease-free survival (DFS) (38.6% vs. 67%, p = 0.005). There were no differences in OS, DFS or NRM between MDR1 C1236T- and C3435T-matched and -mismatched groups. Subgroup analysis suggested that within the matched MDR1 G2677TA group, male gender, haematopoietic cell transplantation-specific comorbidity index ≥1, serum creatinine >137.2 µmol/L and post-transplantation thrombocytopenia were associated with poor survival. Our results demonstrated that patients receiving matched MDR1 G2677TA allo-HSCT experienced a poorer prognosis compared with the mismatched group. The potential mechanism may involve increased expression of P-glycoprotein, leading to decreased accumulation of antimicrobial agents and ultimately contributing to the progression of inflammation. This identification of MDR1 G2677TA genotype compatibility holds promise as a valuable molecular tool for selecting donors for allo-HSCT.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP , Genotipo , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Polimorfismo de Nucleótido Simple , Donantes de Tejidos , Trasplante Homólogo , Pronóstico , Anciano , Resultado del Tratamiento
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 , Compuestos de Anilina/uso terapéutico , Azacitidina/uso terapéutico , Enfermedades de la Médula Ósea/complicaciones , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Pirazinas/uso terapéutico , Aplasia Pura de Células Rojas/etiología , Sulfonamidas/uso terapéutico
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.
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
6.
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
7.
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
8.
Ann Hematol ; 93(3): 425-35, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23978946

RESUMEN

Bcl-2-associated athanogene 3 (BAG3), a member of BAG family, is shown to sustain cell survival and underlie resistance to chemotherapy in human neoplastic cells. We aimed to determine the exact role and underlying mechanisms of BAG3 in human chronic lymphocytic leukemia (CLL). One hundred human CLL samples and 20 normal B-cell samples from healthy controls were collected. We measured the BAG3 expression in these cells and explored its relationship with known prognostic factors for CLL. The roles of BAG3 in cell apoptosis and migration were evaluated by small interfering RNA-mediated knockdown of BAG3 in primary CLL cells. We showed that BAG3 expression level was increased in CLL cells compared with normal B cells. Moreover, BAG3 expression was particularly upregulated in CD38 positive, unmutated immunoglobulin heavy-chain patients and those with lymphadenopathy and/or splenomegaly. Importantly, patients with increased BAG3 expression level have poor overall survival in subgroups with positive ZAP-70 or those without any "p53 abnormality". In addition, knocking down of BAG3 expression resulted in increased apoptotic ratio and decreased migration in primary CLL cells. Our data indicate that BAG3 is a marker of poor prognostic in specific subgroups of CLL patients and may be a potential therapeutic target for this disease.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/sangre , Biomarcadores de Tumor/sangre , Leucemia Linfocítica Crónica de Células B/metabolismo , Proteínas de Neoplasias/sangre , Regulación hacia Arriba , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Apoptosis , Proteínas Reguladoras de la Apoptosis , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Movimiento Celular , Femenino , Estudios de Seguimiento , Silenciador del Gen , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Células Tumorales Cultivadas , Regulación hacia Arriba/efectos de los fármacos
9.
EJHaem ; 5(4): 757-767, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157627

RESUMEN

Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS-IB-1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, p = 0.045; HR = 3.64, 95%CI 1.40-9.44, p = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

10.
Carcinogenesis ; 33(7): 1294-301, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22610076

RESUMEN

MicroRNAs (miRNAs) have been shown to play critical roles in regulating the progress of leukemia. We performed miRNA expression profile in six Chinese patients with chronic lymphocytic leukemia (CLL), and in peripheral B cells from pooled 30 healthy donors, using a platform containing 866 human miRNAs. The most frequent changes in miRNAs in CLL cells included downregulation of miR-126, miR-572, miR-494, miR-923, miR-638, miR-130a, miR-181a and miR-181b and up-regulation of miR-29a, miR-660, miR-20a, miR-106b, miR-142-5p, miR-101, miR-30b, miR-34a, miR-let-7f, miR-21 and miR-155. Among the miRNAs down-regulated in CLL cells, we showed that miR-181a/b expression levels were significantly lower in poor prognostic subgroups defined by unmutated immunoglobulin heavy chain variable status and p53 aberrations. Furthermore, under-expression of miR-181a and miR-181b was associated with shorter overall survival and treatment-free survival in CLL patients. We further evaluated fludarabine-induced apoptosis after transfection of primary CLL cells from 40 patients with miR-15a, miR-16-1, miR-34a, miR-181a and miR-181b mimics. Transfection of miR-34a, miR-181a and miR-181b mimics into CLL cells from p53 wild-type patients led to significant increase in apoptosis compared with miRNA control. However, enforced expression of these miRNAs had no effect on B-CLL cells from p53-attenuated patients. We further demonstrated that miR-181a and miR-181b inhibiting BCL-2, MCL-1 and X-linked inhibitor of apoptosis protein by direct binding to 3'UTR. Thus, these results suggest that miR-181a/b may play important roles in the pathogenesis of CLL and may provide a possible therapeutic avenue and a sensitive indicator of the activity of the p53 axis in CLL.


Asunto(s)
Apoptosis/genética , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , MicroARNs/genética , Antineoplásicos/uso terapéutico , Perfilación de la Expresión Génica , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
11.
Int J Cancer ; 130(9): 2054-61, 2012 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-21647873

RESUMEN

A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. The MDM2 SNP309 genotypes in 173 CLL patients and 260 healthy controls were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, which was confirmed by direct DNA sequencing. Compared with the T/T genotype, the SNP309 G/G genotype instead of T/G heterozygote was associated with a significantly increased risk of CLL (OR = 2.84; 95% CI 1.61-5.03; p < 0.001). Age at onset of CLL was similar irrespective of MDM2 status. MDM2 mRNA expression within CLL of G/G genotype was significantly higher than that in T/G (p = 0.009) and T/T genotypes (p < 0.001). Excluding patients with p53 deletions or mutations enhanced the significance of the findings (G/G vs. T/T, p < 0.001; G/G vs. T/G p = 0.001), which prompted us to study the role of the polymorphism in p53 wild-type individuals. In the p53 wild-type groups, survival analysis showed that the patients with MDM2 SNP309 G/G and T/G genotypes both had significantly shorter treatment-free survival (TFS) than SNP309 T/T genotype. Notably, univariate and multivariate analyses showed that MDM2 SNP309 genotypes were associated with TFS. These data show that MDM2 309G polymorphisms contribute to the risk of developing CLL. The unfavorable MDM2 SNP309 G/G genotype was associated with an increase of MDM2 mRNA expression. MDM2 SNP309 was found to be associated with TFS in p53 wild-type Chinese CLL populations.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Heterocigoto , Humanos , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , ARN Mensajero/genética , Factores de Riesgo , Eliminación de Secuencia
12.
Cancer Sci ; 103(5): 875-81, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22320315

RESUMEN

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Alterations in microRNAs (miRNAs) expression have been proposed to play a role in CLL pathogenesis. Dicer and Drosha are the main regulators of miRNA biogenesis, and deregulation of their expression has been indicated as a possible cause of miRNA alterations observed in various cancers. To investigate the role of Dicer and Drosha in CLL, we assessed the expression of Dicer and Drosha and their correlation with other prognostic factors, including Binet stages, immunoglobulin heavy chain variable gene (IGHV) mutation status, TP53 mutation status, ZAP-70 protein and CD38 expression level in 165 CLL patients by using real-time polymerase chain reaction methods. Patients with unmutated IGHV genes had significantly lower expression of Dicer than patients with IGHV mutations. The lower expression level of Dicer was also significantly associated with higher level of CD38 and ZAP-70, and more aggressive Binet stage. We also analyzed Dicer expression in different cytogenetic subgroups. Lower Dicer level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22.3) in contrast to higher level in good risk cytogenetics (deletion in 13q14 as the sole abnormality). Furthermore, the lower expression of Dicer in CLL shows a strong association with shorter overall survival (OS) (P = 0.0046) as well as with reduced treatment free survival (TFS) (P = 0.0006). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of CLL.


Asunto(s)
ARN Helicasas DEAD-box/genética , Leucemia Linfocítica Crónica de Células B/genética , Ribonucleasa III/genética , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Supervivencia sin Enfermedad , Regulación hacia Abajo , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Pronóstico
13.
Ann Hematol ; 91(4): 553-9, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21987025

RESUMEN

MicroRNAs (miRNAs) are regulatory RNA molecules that are deregulated in many disease types, including cancer. Recently, miRNAs have shown promise as markers for cancer diagnosis. The aim of this study was to investigate whether serum miRNAs can be used as biomarkers for the detection of diffuse large B cell lymphoma (DLBCL). We measured the levels of miRNAs (miR-15a, miR-16-1, miR-21, miR-29c, miR-34a, miR-155, and miR-223) in serum samples from patients with DLBCL and healthy controls using real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We show here that miRNAs are present in human serum in a remarkably stable form. Four of miRNAs (miR-15a, miR-16-1, miR-29c, and miR-155) were significantly elevated in DLBCL serum when compared with normal controls (P < 0.05), while miR-34a was downregulated in DLBCL serum when compared with controls (P < 0.05). Receiver operating characteristic analyses reflects strong discriminating DLBCL from controls, with area under the curves of 0.7722, 0.7002, 0.6672, 0.8538, and 0.7157 for miR-15a, miR-16-1, miR-29c, miR-34a, and miR-155, respectively. At the cut-off value of 0.0006 for miR-15a, the sensitivity was 80% and the specificity was 76%; at the cut-off value of 0.0886 for miR-16-1, the sensitivity was 94% and the specificity was 51%; at the cut-off value of 1.395 for miR-34a, the sensitivity was 100% and the specificity was 70%; at the cut-off value of 0.0022 for miR-155, the sensitivity was 83% and the specificity was 65%. In conclusion, these data suggest that serum miRNAs are potentially useful tools as novel noninvasive biomarker for the diagnosis of DLBCL.


Asunto(s)
Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/genética , MicroARNs/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Curva ROC , Adulto Joven
14.
Onkologie ; 35(5): 268-71, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22868506

RESUMEN

BACKGROUND: Genetic background and environmental factors play an interactive role in the development of acute lymphocytic leukemia (ALL), and the human leukocyte antigen (HLA) system was noted as an important genetic factor in ALL. MATERIAL AND METHODS: Due to the high diversity of HLA alleles, our present study assessed the possibility of an association of HLA molecules in ALL patients living in Jiangsu Province, Eastern China. HLAA, -B, and -DRB1 allele distributions in 156 ALL patients (aged 3-54 years) were analyzed and compared with unrelated healthy hematopoietic stem cell donors from the same ethnic and geographic background. RESULTS: No significance was found at HLA-A, -B loci between the ALL group and the control group. However, a significant difference was discovered at HLA-DRB1*14 (8.65% in the ALL group versus 4.8% in the control group, pC < 0.05), with an odds ratio of 1.87 (95% confidence interval 1.26- 2.80). CONCLUSION: HLA-DRB1*14 may be associated with susceptibility to ALL acquisition among the Jiangsu Han population.


Asunto(s)
Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Cadenas HLA-DRB1/genética , Polimorfismo de Nucleótido Simple/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Medición de Riesgo , Adulto Joven
15.
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
16.
Int J Cancer ; 128(9): 2192-201, 2011 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-20635386

RESUMEN

Complement deficiencies have been identified in many chronic lymphocytic leukemia (CLL) patients. Supplying fresh frozen plasma (FFP)-derived complement can enhance complement-dependent cell lysis by the rituximab. The objective of our study was to evaluate the clinical efficacy and safety of the treatment by adding FFP to rituximab in fludarabine refractory CLL patients. Twenty-two patients were treated with two units of FFP followed with rituximab, 375 mg/m(2), as a single agent, repeated every 1-2 weeks. Patients received a median of four courses of the combined FFP and rituximab treatment (range: 2-6). Sixteen patients (72.7%) responded to treatment and seven (31.8%) achieved a complete remission. Three (13.6%) of which had no evidence of minimal residual disease after treatment. Patients with high expression of ZAP-70 or CD38, unmutated immunoglobulin heavy chain variable region, mutated p53, or adverse cytogenetic features, achieved response to treatment at rates that appeared similar to those who did not have such characteristics. With a median follow-up of 12 (4-19) months, the median overall survival and progression free survival have not been achieved. Toxicity was minimal, and the treatment was well tolerated. Our data suggest that the adding FFP to rituximab is an effective nonmyelotoxic regimen for the treatment of fludarabine refractory CLL patients.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antineoplásicos/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Plasma , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Rituximab , Terapia Recuperativa/métodos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
17.
Ann Hematol ; 90(6): 709-17, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21113594

RESUMEN

The poor prognosis of chronic lymphocytic leukemia (CLL) patients with del(17p13) is well established. Several studies have shown that cases with TP53 mutations and TP53 mutations without del(17p13) may be adverse prognostic factors. We studied 173 well-characterized CLL patients by direct sequencing to detect TP53 mutations (exons 2-11). TP53 mutations were detected in 14.5% (25 of 173) of samples. Most patients with del(17p13) had TP53 mutations (72.2%). Mutations in the absence of del(17p13) were found in 8.3% in our cohort, which were higher than other countries. Compared with cases without TP53 alterations, TP53 mutations and deletions were both associated with advanced stages and unmutated immunoglobulin heavy-chain variable region status. Survival analysis showed that the occurrence of TP53 mutations and del(17p13) were associated with shorter overall survival (OS), treatment-free survival (TFS), and resistance to chemotherapy. TP53 mutations were the variables strongly associated with OS and TFS by multivariate Cox regression analysis. Moreover, we also found that cases with TP53 mutations in the absence of del(17p13) had a similar clinical and biological course and similar poor short OS as cases carrying del(17p13) in Chinese patients with CLL.


Asunto(s)
Pueblo Asiatico/genética , Deleción Cromosómica , Cromosomas Humanos Par 17 , Leucemia Linfocítica Crónica de Células B/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Cromosomas Humanos Par 17/genética , Estudios de Cohortes , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/etnología , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Mutación/fisiología , Pronóstico , Análisis de Supervivencia
18.
Eur J Haematol ; 86(5): 442-6, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21447089

RESUMEN

T(15;17) is the most common chromosomal aberration in patients with acute promyelocytic leukemia (APL), leading to the formation of PML-RARα fusion gene. In a small subset of patients with APL, the RARα gene is fused with different partners. Here, we report a rare APL case with STAT5B-RARα fusion transcript. Cytomorphologic and immunophenotypic analyses showed typical features of APL. However, cytogenetic analysis showed normal karyotype, and interphase fluorescence in situ hybridization (FISH) showed PML-RARα negative. Quantitative RT-PCR also showed PML-RARα negative but STAT5B-RARα positive and sequencing analysis confirmed the result. Molecular markers including FLT3, NPM1, c-Kit and C/EBPα mutation were all negative. To our knowledge, this is the first APL patient with STAT5B-RARα in Chinese population and the fifth patient around the world according to published paper.


Asunto(s)
Leucemia Promielocítica Aguda/genética , Proteínas de Fusión Oncogénica/genética , Factor de Transcripción STAT5/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Secuencia de Bases , Proteína alfa Potenciadora de Unión a CCAAT/genética , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Trasplante de Células Madre Hematopoyéticas , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Promielocítica Aguda/terapia , Masculino , Mutación , Proteínas Nucleares/genética , Nucleofosmina , Proteínas Proto-Oncogénicas c-kit/genética , Tirosina Quinasa 3 Similar a fms/genética
19.
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.

20.
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
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