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Leuk Lymphoma ; : 1-6, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32476519


In order to explore the prognostic value of CD2, CD4, and human leucocyte antigen-DR (HLA-DR) expression and Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in leukemia cells in the bone marrow of patients with acute promyelocytic leukemia (APL), we retrospectively collected and analyzed the immunophenotype, molecular features and clinical characteristics of 219 newly diagnosed adult patients with APL in Henan Provincial People's Hospital from January 2010 to December 2019. It turned out that the relapse rates of patients with CD2, CD4, or HLA-DR expression and the early mortality rates of patients with CD2 expression, HLA-DR expression, or FLT3-ITD mutation were higher than those of their counterparts. Moreover, reduced overall survival was found for patients who showed CD2 expression, HLA-DR expression or FLT3-ITD mutation. Therefore, CD2 expression, HLA-DR expression and FLT3-ITD mutation were adverse prognostic factors in adults with APL.

Clin Lymphoma Myeloma Leuk ; 20(7): e382-e391, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32336675


INTRODUCTION: The purpose of this study was to explore the outcomes of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) plus idarubicin (IDA) as a frontline treatment in adult patients with acute promyelocytic leukemia (APL). PATIENTS AND METHODS: We analyzed the outcomes of ATRA and intravenous ATO plus IDA as a frontline induction therapy in 118 patients with APL with high-risk (HR) and standard-risk (SR) disease from January 2008 to December 2017. The medical records of 118 patients with APL (HR, n = 45; SR, n = 73) who received the frontline triple combination regimen at Henan Provincial People's Hospital and Tongji Hospital were retrospectively reviewed. Consolidation therapy comprised 6 cycles of ATO and ATRA plus IDA, and IDA was administered in 1 to 4 cycles of consolidation therapy based on the comparable clinical efficacy compared with 6 cycles and fewer side effects to myocardium without subsequent maintenance therapy. RESULTS: Of 118 patients, there were 3 (2.5%) early deaths and 115 (97.5%) hematologic complete remissions; 102 (88.7%) of 115 patients achieved molecular complete remission following induction therapy, and all patients were polymerase chain reaction-negative for promyelocytic leukemia-retinoic acid receptor alpha after the first cycle of consolidation therapy. The 5-year overall survival (OS) and event-free survival (EFS) were 93.0% ± 2.9% and 92.4% ± 3.0%, respectively. Early death, hematologic complete remissions, molecular complete remissions, and toxicities were comparable between the HR and SR groups. The cumulative incidence of relapse in the HR group was 4.7% (n = 2), and the cumulative incidence of relapse in the SR group was 0. The OS and EFS of the SR and HR groups were comparable (92.3% ± 4.5% vs. 92.8% ± 4.0%; X2 = 0.263; P = .608; 92.3% ± 4.5% vs. 91.1% ± 4.2%, X2 = 0.917; P = .338). The total dosage of IDA was approximately 181 to 258 mg, and no patient experienced cardiotoxicity. OS and EFS were not influenced by fms-related tyrosine kinase 3 internal tandem duplication mutation status (P = .405 and P = .528, respectively). CONCLUSION: The triple combination of ATRA and ATO plus IDA as both an induction and consolidation therapy for the HR and SR groups attained excellent outcomes, and this regimen was effective, safe, and easy, without maintenance therapy. The triple combination treatment might be a preferred frontline therapy for patients with APL, especially for those with HR or the APL fms-related tyrosine kinase 3 internal tandem duplication mutation.

J Cell Physiol ; 235(4): 3790-3797, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31613009


Acute myelocytic leukemia (AML) is an aggressive malignant tumor and typically fatal without treatment. Identification and development of novel biomarkers could be beneficial for the diagnosis and prognosis of AML patients. Here, we aimed to identify the accurate DNA methylation prognostic signatures for AML patients. The DNA methylation data of AML patients and corresponding clinical information were retrieved from The Cancer Genome Atlas database. CPG sites that correlates closely with the survival of the AML patients were identified and further combined into CPG sites pairs to screen the survival-related pairs. The prognostic signatures were identified by the C-index and forward search algorithms and validated by the verification group. Finally, the functional enrichment analysis was performed on these CPG sites. As a result, a total of 498 CPG sites associated with the overall survival of AML patients was obtained. A prognostic signature composed of 10 CPG sites pairs was obtained and validated. The functional enrichment analysis showed prognostic genes were mainly enriched in tumor protein processing, cell differentiation, blood leukocyte immunity, and platelet growth factor pathways. In summary, we identified two accurate prognostic methylation signatures (NDRG2 and TLR7), which would be served as a novel therapy target for AML.

Cell Cycle ; 18(14): 1660-1669, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31204563


Background: Nowadays, microRNAs (miRNAs) attract much attention in regulating anticancer drug resistance in cancers including multiple myeloma (MM). Bortezomib is the first-line choice in MM treatment, and bortezomib resistance caused by aberrant DNA repair leads to the recurrence and therapeutic failure of MM. Objective: Our study aims to identify a miRNA that overcomes bortezomib resistance in MM. Methods: We established bortezomib-resistant MM cell lines, and screened several miRNAs that have aberrant expressions in MM cell lines. The expression of DNA-repair-related proteins were assessed by western blot, and cell viability was determined by the MTT assay in bortezomib-resistant cell lines. The binding between miRNAs and 3'-UTR of APE1 mRNA was confirmed by luciferase reporter assay. The mouse bortezomib-resistant xenograft was established to verify the therapeutic effect of miRNA overexpression. Results: miR-520g and miR-520h were significantly downregulated in bortezomib-resistant MM cell lines, and overexpression of miR-520g and miR-520h together inhibited expression of homologous recombination-related protein Rad51 and cell viability of bortezomib-resistant MM cells in vitro by binding with 3'-UTR of APE1 mRNA. Combined overexpression of miR-520g and miR-520h inhibited bortezomib-resistant MM tumor growth in vivo. Conclusion: Our findings demonstrated that combined overexpression of miR-520g and miR-520h overcomes bortezomib resistance in MM through inhibition of DNA repair, offering a promising therapeutic target for MM treatment.

Biol Blood Marrow Transplant ; 25(5): 975-980, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30658223


We compared the outcomes of immunosuppressive therapy (IST) with those of T cell-replete haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) in children and adolescents with severe aplastic anemia (SAA). The medical records of 49 patients with SAA who received frontline IST (n = 29) or frontline haplo-HSCT (n = 20) between 2012 and 2016 were analyzed retrospectively. Fourteen patients responded after the first IST, and 1 patient responded after the second IST in the frontline IST group; 12 patients underwent salvage HSCT after IST failure. Sixteen of the 20 patients who underwent frontline haplo-HSCT survived without treatment failure. The 3-year overall survival of the frontline IST group was comparable to that of the frontline haplo-HSCT group (79.3 ± 7.5% versus 85.0 ± 8.0%; χ2 = 0.110; P = .740). The 3-year failure-free survival was lower in the frontline IST group compared with the frontline haplo-HSCT group (35.9 ± 10.9% versus 80.0 ± 8.9%; χ2 = 4.089; P = .043). Five patients of the IST group who underwent salvage HSCT achieved long survival without event. The event-free survival was lower in the salvage HSCT group compared with the haplo-HSCT group (41.7 ± 14.2% versus 80.0 ± 8.9%; χ2 = 3.992; P = .046), and the incidences of acute GVHD, grade II-IV acute GVHD, chronic GVHD, and severe infection were comparable between the 2 groups. Our results suggest that frontline haplo-HSCT may be a better treatment than IST for children and adolescents with SAA who lack an HLA age-matched familial donor.

Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressão/métodos , Terapia de Salvação/métodos , Transplante Haploidêntico/métodos , Adolescente , Anemia Aplástica/mortalidade , Criança , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunossupressão/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Haploidêntico/mortalidade , Transplante Haploidêntico/normas , Resultado do Tratamento