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RATIONALE: Patients with relapsed and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation are at higher risk of relapse and have shorter overall survival. PATIENT CONCERNS: A 31-year-old man presented to the hematology department with intermittent fever and pancytopenia. He was diagnosed with Ph+ acute lymphoblastic leukemia and experienced 2 relapses during treatment. A drug-resistant T315I mutation was detected in the ABL kinase region during review. DIAGNOSES: Morphological examination of the bone marrow revealed approximately 93.5% lymphoid blast. Flow cytometric analysis confirmed the diagnosis of common B-cell ALL with the following phenotype: CD34, CD45dim, CD19, CD10, cCD79a, CD58dim, CD81dim, cTdT, HLA-DR, CD22dim, CXCR4, CD33dim, CD20, CD25, CD13, CD123. The examination of the ABL kinase region mutation suggested a T315I mutation. INTERVENTIONS: Olverembatinib, a third-generation TKI drug, was administered in combination with inotuzumab ozogamicin to treat the disease. OUTCOMES: The patient achieved morphological remission with a negative flow cytometry MRD test, and the quantification of BCR-ABL transcripts was 0% after 1 cycle of therapy. LESSONS: The third-generation TKI olverembatinib has been proven to be effective in CML patients with the T315I mutation, and it may also be effective in Ph+ acute lymphoblastic leukemia. Some new immune drugs have also shown improvement in the remission rate. Combination therapy with olverembatinib and Ino can achieve a complete molecular response in patients with relapsed and refractory Ph+ ALL with the T315I mutation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Inotuzumab Ozogamicina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Adulto , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomo Filadélfia , MutaçãoRESUMO
Acute myeloid leukemia (AML) with NPM1 mutation is a distinct genetic entity with favorable outcomes. Nevertheless, emerging evidence suggests that NPM1-mutated AML is still a highly heterogeneous disorder. In this study, 266 patients with AML with NPM1 mutations were retrospectively analyzed to evaluate the associations between variant allele frequency (VAF) of NPM1 mutations, co-mutated genes, measurable residual disease (MRD), and patient outcomes. Multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RT-PCR) were used for monitoring MRD. Ultimately, 106 patients were included in the long-term follow-up period. Patients with high NPM1 VAF (≥ 42.43%) had poorer 2-year relapse-free survival (RFS) (55.7% vs. 70.2%, P = 0.017) and overall survival (OS) (63.7% vs. 82.0%, P = 0.027) than those with low VAF. DNMT3A mutations negatively influenced the outcomes of patients with NPM1 mutations. Patients with high DNMT3A VAF or NPM1/DNMT3A/FLT3-ITD triple mutations had shorter RFS and significantly lower OS than that in controls. After two cycles of chemotherapy, patients with positive MFC MRD results had lower RFS (MRD+ vs. MRD-:44.9% vs. 67.6%, P = 0.007) and OS (61.5% vs. 76.6%, P = 0.011) than those without positive MFC MRD results. In multivariate analysis, high NPM1 VAF (hazard ratio [HR] = 2.045; P = 0.034) and positive MRD after two cycles of chemotherapy (HR = 3.289; P = 0.003) were independent risk factors for RFS; MRD positivity after two cycles of chemotherapy (HR = 3.293; P = 0.008) independently predicted the OS of the patients. These results indicate that VAF of both NPM1 gene itself or certain co-occurring gene pre-treatment and MRD post-treatment are potential markers for restratifying the prognoses of patients AML having NPM1 mutations.
Assuntos
Leucemia Mieloide Aguda , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Nucleofosmina , Estudos Retrospectivos , Citometria de Fluxo , Prognóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Recidiva , Mutação , Neoplasia Residual/genéticaRESUMO
Accurately predicting the survival prospects of patients suffering from pancreatic adenocarcinoma (PAAD) is challenging. In this study, we analyzed RNA matrices of 182 subjects with PAAD based on public datasets obtained from The Cancer Genome Atlas (TCGA) as training datasets and those of 63 subjects obtained from the Gene Expression Omnibus (GEO) database as the validation dataset. Genes regulating the metabolism of PAAD cells correlated with survival were identified. Furthermore, LASSO Cox regression analyses were conducted to identify six genes (XDH, MBOAT2, PTGES, AK4, PAICS, and CKB) to create a metabolic risk score. The proposed scoring framework attained the robust predictive performance, with 2-year survival areas under the curve (AUCs) of 0.61 in the training cohort and 0.66 in the validation cohort. Compared with the subjects in the low-risk cohort, subjects in the high-risk training cohort presented a worse survival outcome. The metabolic risk score increased the accuracy of survival prediction in patients suffering from PAAD.
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BACKGROUND: Holobionts comprising nitrogen-fixing diazotrophs and phytoplankton or zooplankton are ubiquitous in the pelagic sea. However, neither the community structure of plankton-associated diazotrophs (PADs) nor their nitrogenase transcriptional activity are well-understood. In this study, we used nifH gene Illumina sequencing and quantitative PCR to characterize the community composition and nifH expression profile of PADs with > 100 µm size fraction in the euphotic zone of the northern South China Sea. RESULTS: The results of DNA- and RNA-derived nifH gene revealed a higher alpha-diversity in the active than in the total community. Moreover, the compositional resemblance among different sites was less for active than for total communities of PADs. We characterized the 20 most abundant OTUs by ranking the sum of sequence reads across 9 sampling stations for individual OTUs in both nifH DNA and RNA libraries, and then assessed their phylogenetic relatedness. Eight of the 20 abundant OTUs were phylogenetically affiliated with Trichodesmium and occurred in approximately equal proportion in both the DNA and RNA libraries. The analysis of nifH gene expression level showed uneven attribute of the abundance and nitrogenase activities by the remaining 12 OTUs. Taxa belonging to cluster III and Betaproteobacteria were present at moderate abundance but exhibited negligible nitrogenase transcription activity. Whereas, the abundances of Richelia, Deltaproteobacteria and Gammaproteobacteria were low but the contribution of these groups to nitrogenase transcription was disproportionately high. CONCLUSIONS: The substantial variation in community structure among active dizatrophic fractions compared to the total communities suggests that the former are better indicators of biological response to environmental changes. Altogether, our study highlights the importance of rare PADs groups in nitrogen fixation in plankton holobionts, evidenced by their high level of nitrogenase transcription.
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Bactérias/isolamento & purificação , Proteínas de Bactérias/genética , DNA Bacteriano/genética , Nitrogenase/genética , Plâncton/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , China , Fixação de Nitrogênio , Filogenia , Água do Mar/microbiologiaRESUMO
BACKGROUND: Hypereosinophilic syndrome (HES) can be fatal, particularly when eosinophils infiltrate vital organs and/or if extensive thrombosis develops. However there are no standard recommendations for the use of anticoagulant therapy of HES in the setting of thrombosis. METHODS: We herein present a case of a 46-year-old female who presented with marked peripheral eosinophilia with symptoms of multi-organ infiltration and extensive deep venous thrombosis (DVT). In this case, evaluation was carried out before the diagnosis was established, and timely standard-dose corticosteroids combined with a new oral anticoagulant (NOAC) therapy were carried out. RESULTS: These measures resulted in a rapid response and long-term disease control. CONCLUSION: Although there are no data to support which anticoagulant is preferred in this setting, this case indicates that the new oral anticoagulants may play an important role in the treatment of thrombosis in HES.
Assuntos
Anti-Inflamatórios/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/tratamento farmacológico , Prednisolona/uso terapêutico , Rivaroxabana/uso terapêutico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Terapia Combinada , Feminino , Humanos , Síndrome Hipereosinofílica/patologia , Rim/patologia , Fígado/patologia , Pessoa de Meia-Idade , Transfusão de Plaquetas , Tórax/patologiaRESUMO
CCAAT/enhancer binding protein alpha gene (CEBPA) is an important transcription factor in maintenance of differentiation of granulocyte series of hematopoietic system. It plays a key role in regulating cell proliferation and differentiation. CEBPA mutation easily occurs in M1 and M2 type of acute myeloid leukemia, about 5%-14% in adult acute myeloid leukemia and 7.9% in children with acute myeloid leukemia. At present, domestic CEBPA mutation research is far less than abroad. This review focuses on the structual characteristics and detection method of CEBPA, CEBPA clinical features, the effect of CEBPA mutation on the prognosis of patients and the choice of treatment.
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Leucemia Mieloide Aguda , Mutação , Proteínas Estimuladoras de Ligação a CCAAT , Humanos , PrognósticoRESUMO
Bacterial metabolism plays a dual role [bacterial production (BP) and bacterial respiration (BR)] in the aquatic ecosystem and potentially leads to hypoxia in the coastal eutrophic area. Bacterial growth efficiency (BGE) is an important index showing the contribution of bacterial metabolism to marine biological production and carbon budget in the pelagic ecosystem. In this study, the spatial and seasonal variety as well as diurnal variation dynamics of BGE and associated ecological characteristics were investigated in a partly eutrophicated subtropical bay (the Daya Bay) located in the northern South China Sea. Furthermore, the relationship between bacterial metabolism and potential hypoxia event was analyzed. The average BGE was 0.14 and 0.22 in summer and winter, respectively, which was lower than the mean value ever reported in other coastal and estuarine waters. The diurnal variations of BGE and BP were widely fluctuated in the Daya Bay, with approximately 3-8 fold variation of BP and 2-3 fold variation of BR in different seasons, suggesting the importance of short-term ecological dynamics on evaluating the long-term ecological processes in the coastal waters. BR was the predominant contributor to the bacterial carbon demand; however, the variation of BGE was controlled by BP in both seasons. BGE was always high in the near-shore waters with higher eutrophic level and more active BP and BR. The bacterial metabolism could deplete dissolved oxygen (DO) in the Daya bay within about 9 days when the water body was enclosed and photosynthesis was prohibited. Therefore, low DO concentration and potential hypoxia was more likely to be found in the near-shore waters of the Daya Bay in summer, since the water was stratified and enclosed with poor water exchange capacity in this area. While in winter, hypoxia seldom occurred due to vertical mixing throughout the water column. Further biological-physical coupling research is recommended to find out the detailed formation mechanism of hypoxia in the bay, and to predict the potential hypoxia events and their environmental impacts in the future.
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Bactérias/crescimento & desenvolvimento , Baías/microbiologia , Eutrofização , Anaerobiose , Bactérias/efeitos dos fármacos , China , Ecossistema , Estações do AnoRESUMO
This study was aimed to explore the clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutations. Fifty-five de novo AML patients with normal karyotype were retrospectively analyzed with regard to frequency of CEBPA mutation, clinical characteristics and therapeutic response. The results showed that CEBPA mutation was detected in 20 patients (36.4%), among them 17 cases displayed double mutations, three cases were with single mutation. The clinical characteristics of patients with CEBPA mutation displayed as follows: 75% of AML patients with CEBPA mutation were AML-M1 and AML-M2, the hemoglobin level at newly diagnosis was higher and the platelet count at newly diagnosis time was lower than those of AML patients without CEBPA mutation [(98.30 ± 20.33) g/L vs (81.69 ± 23.74) g/L (P < 0.05); and (33.30 ± 38.27) ×10(9)/L vs (64.79 ± 61.60) ×10(9)/L (P < 0.05)]. The leukemic cells highly expressed CD7 and CD34. The therapeutic efficacy of 1 cycle for AML patients with CEBPA mutation was satisfactory (72.2%), was higher than that of patients without CEBPA mutation(68.6%), but there was no statistical significance (P > 0.05). It is concluded that AML with CEBPA mutation is more observed in AML-M1 and AML-M2, and accompanies by high level of hemoglobin and lower platelet count, expression of CD7 and CD34. Early-term therapeutic efficacy is satisfactory. The frequency of CEBPA mutation may be higher in Chinese patients with AML compared with that reported in Western world.
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Proteínas Estimuladoras de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/genética , Mutação , Adolescente , Adulto , Criança , Feminino , Humanos , Cariótipo , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: The present study aimed to examine the cytogenetic and genetic mutation features of acute myeloid leukemia (AML) in elderly Chinese patients. METHODS: A retrospective analysis of cytogenetics and genetic mutations was performed in 113 cases (age range 50-82 years) with de novo AML. RESULTS: The most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0% (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89% (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88% (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%, respectively (χ2 = 0.704, P = 0.703) based on risk stratification. CONCLUSION: Cytogenetics and genetic mutations alone may not be sufficient to evaluate the prognoses of elderly AML patients. The search for a novel model that would enable a more comprehensive evaluation of this population is therefore imperative.
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Povo Asiático/genética , Biomarcadores Tumorais/genética , Aberrações Cromossômicas , Análise Citogenética/métodos , Leucemia Mieloide Aguda/genética , Mutação/genética , Idoso , Idoso de 80 Anos ou mais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Nucleofosmina , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Fatores de Risco , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
Certain molecular mutations are associated with signs of cell morphology and differentiation in acute myeloid leukemia (AML). However, only limited data are available for the detailed analysis of such correlations. In this study, AML patients were classified into 4 subsets according to CD34, HLA-DR and CD11c expression levels. Significantly low CD34 antigen expression was observed in nucleophosmin (NPM1)-mutated patients and in those with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). No correlations were observed among NPM1 mutations, FLT3-ITD and monocytic morphology in patients without CD34 expression. Both NPM1 mutations and FLT3-ITD were absent in cluster IIb patients (CD34(+)CD11c(-)). The associations among NPM1 mutations, FLT3-ITD and the surface molecular signature of leukemic cells may offer beneficial information about the pathogenesis of AML.
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Leucemia Mieloide Aguda/genética , Mutação , Proteínas Nucleares/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/metabolismo , Antígeno CD11c/metabolismo , Criança , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/classificação , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Sequências de Repetição em Tandem , Adulto JovemRESUMO
OBJECTIVES: To explore NPM1, FLT3-ITD, CEBPA, and c-kit mutations in patients with acute myeloid leukemia (AML) from Chinese population. METHODS: In this study, we retrospectively analyzed the prevalence and clinical proï¬le of NPM1, FLT3-ITD, CEBPA, and c-kit mutations in 312 patients with de novo AML. RESULTS: The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 15.4, 14.0, 7.64, and 25.6%, respectively. The occurrence rate of NPM1 mutations increased with age in patients younger than 60 years. NPM1, c-kit, and CEBPA mutations were all associated with French-American-British subtypes. Patients with NPM1 mutations and FLT3-ITD presented with higher peripheral white blood cell counts and marrow blast percentages. CONCLUSION: Both this and previous studies may suggest low frequencies of NPM1 and FLT3-ITD mutations in AML patients from the Chinese population, and they may have a synergistic function in stimulating proliferation of leukemia cells.
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Proteínas Estimuladoras de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas c-kit/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Adulto JovemRESUMO
This article reviews particular subgroup of B-cell lymphoma, called "double-hit" lymphoma (DHL) because of its distinct aberrations-related genes influencing various processes such as apoptosis, differentiation, and proliferation. Recent studies indicate that tumorigenesis is a complex process involving multiple genes, genetic abnormalities, including gene mutations, deletions, and chromosomal alterations. Chromosomal aberrations are not affecting only basic cellular life preserving activities such as cell proliferation, differentiation, apoptosis, and signal transduction, but are also indispensible for evaluation of lymphoma occurrence, progression, and prognosis as well differential diagnosis and other aspects assessment. DHL is group accompanied by IGH-BCL2 and MYC rearrangement, behaving highly aggressively, with a complex and distinct karyotype which can not be extrapolated solely by morphological pathological assessment, since it has not been entirely characteristic. Therefore, we are reviewing possible effects of multiple genetic rearrangements, particular genes mutations, and developing hypothesis due which pathophysiology mechanisms DHL accomplish synergistic malignant potential.
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Linfoma de Células B/genética , Aberrações Cromossômicas , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Rearranjo Gênico , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Linfoma de Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6 , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismoRESUMO
OBJECTIVES: To explore the relationships between age, cytogenetic subgroups, molecular markers, and cells with leukemic aberrant immunophenotype in patients with acute myeloid leukemia (AML). METHODS: In this study, we evaluated the correlations between age, cytogenetic subgroups (normal, balanced and unbalance karyotype), molecular mutations (NPM1, FLT3-ITD, and CEBPA mutations) and marrow leukemia cells (LC) identified by flow cytometry in 256 patients with de novo AML. RESULTS: From age group 10-19 years to age group ≥ 60 years, the percentage of LC decreased from 67.0 ± 18.4% to 49.0 ± 25.1% (F = 2.353, P = 0.041). LC percentage was higher in patients with balanced karyotypes (65.7 ± 22.4%), than those with unbalanced karyotypes (46.0 ± 26.6%) (u = 3.444, P = 0.001) or a normal karyotype (49.9 ± 22.1%) (u = 5.093, P < 0.001). Patients with FLT3-ITD (64.3 ± 19.5%) had higher LC percentages compared with those without (54.2 ± 24.3%) (u = 2.794, P = 0.007). CONCLUSIONS: Associations between age, cytogenetics, molecular markers, and marrow leukemia cells may offer beneficial information to understand the biology and pathogenesis of AML.
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Medula Óssea/patologia , Proteínas Estimuladoras de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/genética , Mutação/genética , Proteínas Nucleares/genética , Sequências de Repetição em Tandem/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Análise Citogenética , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , Sensibilidade e Especificidade , Adulto JovemRESUMO
This study was aimed to investigate the correlation of NPM1 and FLT3-ITD mutations with leukocyte count in peripheral blood and bone marrow blasts in patients with acute myeloid leukemia (AML). Fifty-one acute myeloid leukemia patients with normal karyotype from January 2009 to December 2011 were enrolled in this study. The clinical data of 51 cases were analyzed retrospectively. Out of 52 cases 22 were male, and 29 were female. The median age was 47 years old (ranged from 14 to 83 years old). The de novo patients were examined by bone marrow cytomorphology and blood routine analysis. Polymerase chain reaction was used to analyze the NPM1 and FLT3-ITD mutations. The results showed that the patients with NPM1 mutations had higher leukocyte count compared with those without mutations (30.7×10(9)/L vs 8.6×10(9)/L, P = 0.002). FLT3-ITD mutation was related to higher leukocyte count (42.38×10(9)/L vs 11.45×10(9)/L without mutation, P = 0.033) and blasts (74.0% vs 60.25% without mutation, P = 0.036). The leukocyte count and percentage of bone marrow blasts were lowest in the patients with neither mutations, and gradually increasing in the NPM1(-) mutation, FLT3-ITD(-) mutation, and NPM1(+) mutation, FLT3-ITDI(+) mutation, and NPM1(+)/FLT3-ITD(+) mutation groups (P < 0.05). The patients tended to have NPM1 (P = 0.002) and FLT3-ITD (P = 0.033) mutations when their leukocyte counts were more than 12.55×10(9)/L and 37.85×10(9)/L, respectively. Those with bone marrow blast more than 72.25% showed higher rate of FLT3-ITD mutation (P = 0.008). Patients with NPM1 mutations had higher complete remission rate than those without NPM1 mutation (78.13% vs 40.0%, χ(2) = 4.651, P = 0.031) after remission induction therapy. It is concluded that both NPM1 and FLT3-ITD mutations are linked to higher leukocyte count and blast percentage, suggesting that both mutations may be associated with increased proliferation of leukemia cells, and may have a synergistic function in stimulating proliferation.
Assuntos
Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/genética , Mutação , Proteínas Nucleares/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Cariótipo , Cariotipagem , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To analyze the cytogenetic characteristics of different age subgroups in patients with acute myeloid leukemia (AML), and to explore the relationship between age and cytogenetics. METHODS: Between January 2004 and December 2011, Bone marrow (BM) samples from 640 patients with de novo AML were analyzed retrospectively. The analyses were performed according to standard culturing and banding techniques, and clonal abnormalities were defined and described according to the International System for Human Cytogenetic Nomenclature (ISCN 2009). The cytogenetic subtypes were performed as normal, balanced, and unbalanced karyotypes. In the last group, the age distribution of complex and monosome karyotypes were further analyzed. The patients were divided into 8 age groups: 0 - 9, 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, 60 - 69, and ≥ 70 year old groups. RESULTS: The distribution of normal, balanced, and unbalanced karyotypes showed age specific characteristics. The incidence of normal karyotype increased from 6.67% (0 â¼ 9 year old) to 58.33% (≥ 70) (χ(2) = 20.68, P = 0.001) and balanced karyotype decreased from 73.33% (0 â¼ 9) to 11.11% (≥ 70) (χ(2) = 48.22, P < 0.01). The frequency of unbalanced karyotypes increased from 20.0% (0 â¼ 9) to 30.56% (≥ 70) (χ(2) = 18.963, P = 0.008). The frequency of complex karyotype was 6.67% in 0 - 9 year old group, followed by 0% in 10 - 19 and 20 - 29 year old group, and from 1.72% to 11.11% from 30 - 39 to ≥ 70 year old group (χ(2) = 8.341, P = 0.08). Monosome karyotype was only detected in patients in 30 year old or older groups. Although an increased tendency was observed with ages, there was no significant difference (χ(2) = 4.778, P = 0.311). CONCLUSION: The different age profiles of the cytogenetic subtypes may indicate the different mechanisms of the pathogenesis of AML, which may also offer beneficial information for etiological research of AML.
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Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Cariótipo , Cariotipagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
This study was aimed to explore the anti-leukemic effect of scutellaria extract SBX in human leukemia cell lines and its mechanism. The leukemia cell lines, including HL-60, NB4, U937, K562 and Jurkat, were cultured in vitro and proliferative inhibition of these cell lines was detected by CellTiter-Glo Luminescent Cell Viability Assay in order to screen the most sensitive cell line. The effect of SBX on cell cycle was analyzed by flow cytometry and the protein expressions determined by Protein Pathway Array respectively. The results indicated that SBX (10 - 200 µmol/L, for 72 h) significantly inhibited the proliferation of different leukemia cell lines in a dose-dependent manner (r value was 0.86, 0.88, 0.95, 0.94, 0.96, respectively), the HL-60 was the most sensitive cell line. Flow cytometric analysis showed that SBX (50, 10 µmol/L, for 48 h) arrested HL-60 cells in the G(0)/G(1) phase. In addition, protein expression of p-PKC α/ßII, p-p38, Cdc25B, XIAP of HL-60 cells increased, and p-AKT, p-SAPK/JNK, Notch4, Cdk4, Cdc2, cyclin E, Akt, Bcl-2, Bax, cdc42, TNF-α, p27, CaMKKa decreased after exposure to SBX (50 µmol/L, for 48 h). It is concluded that SBX can inhibit the proliferation of different leukemia cell lines, and HL-60 is a sensitive cell line. SBX significantly influences EGFR, Ras/Raf/MAPK and Notch signaling pathway, through which effects the expression of cell cycle-related proteins resulting in arrest of HL-60 cells in G(0)/G(1).
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Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia/tratamento farmacológico , Scutellaria , Transdução de Sinais/efeitos dos fármacos , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Leucemia/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To investigate whether the fetal immune tolerance induction could replace the HLA typing for hematopoietic stem cell transplantation. METHODS: Immune tolerance of SD rats was induced by injecting host Wistar rats peripheral blood mononuclear cells into yolk sac of the embryo, afterward the mature male offsprings were used as donor. The host female recipients received lethal dose irradiation and bone marrow transplantation(BMT). The Wistar rats transplanted with bone marrow from donor and unrelated SD rats as well as the rats which received radiation alone were used as control. The survival, histopathologically GVHD, the mental status, food and water intake, coat characteristics, activities were observed. Forty days after BMT, autologous and allogenous skin transplantation between donor and recipient rats was performed to observe the engraftment of solid organ. RESULTS: The survival of the rats received bone marrow grafts from the immune tolerant donor was significantly longer than that of control groups (30 day survival rates were 86.7%, 6.7%, 0%, and 0% respectively), and there was no histopathologically GVHD observed, while in the sham group, the manifestations of GVHD was clearly visible. The skin engraftment rate between the host and the immune tolerant donor was significantly higher than that among non-related rats (84.6% and 0% respectively). CONCLUSION: The induction of immune tolerance in embryo can overcome the HLA barrier and provide a good donor for hematopoietic stem cell and solid organ transplantation.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Terapia de Imunossupressão , Quimeras de Transplante , Animais , Embrião de Mamíferos/imunologia , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Masculino , Ratos , Ratos Sprague-Dawley , Ratos WistarRESUMO
OBJECTIVE: To search for the characteristics of MFS in corneal morphology and thickness. METHODS: Twenty-four patients (48 eyes) with MFS and 24 healthy age- and gender-matched volunteers (48 eyes) were recruited in this clinical prospective, and comparative series study. Firstly, biomicroscopic examination and Type-A ultrasonometry was conducted to search for ectopia lentis and axis length. Secondly, the corneal morphologic parameter [including the height of anterior and posterior surface, the centre corneal curvature, the mean astigmatism in the 3.0-mm central zone (Mean A), the mean simulated astigmatism (Sim A), the mean keratometry in the 3.0-mm central zone (Mean K), the mean simulated keratometry (Sim K), the 3.0-mm zone irregularity (3.0ZI), the 5.0-mm zone irregularity (5.0ZI), corneal thickness index (CTI)] and thickness (at the central location and at eight midperipheral locations) were obtained by the the autorefractometer and the Orbscan II Z corneal topography. Last, the statistics method including Crosstabs, One-way ANOVA, student-t test and discriminant analysis were applied and the correlations were established. RESULTS: There is no statistically significance between MFS group and control group in ages (38 ± 7) and (37 ± 8) years, gender (8/16) and (9/15), and axis length (23.12 ± 1.06) mm and (24.26 ± 2.96) mm (age χ(2) = 0.091, P = 0.763;gender t = 0.324, axis length t = 1.976, P > 0.05). Flat cornea ratio (66.7% and 12.5%) and topography of the oval (25.0% and 16.7%), irregular bow-shaped (41.7% and 37.5%) and irregular-shaped (12.5% and 8.3%) were increased significantly in patients with MFS. The corneal topography (MFS/control) showed that there are statistically significance in the thinnest thickness of cornea (489.8 ± 42.9)µm and (544.8 ± 25.7)µm, Mean K (40.60 ± 1.30) D and (42.80 ± 1.40) D, Sim K (40.50 ± 1.30) D and (42.80 ± 1.20) D, Sim A (1.08 ± 0.86)D and (0.91 ± 0.46) D, CTI 1.57 ± 0.24 and 1.21 ± 0.14, 3.0ZI (1.76 ± 0.96) D and (1.54 ± 0.82) D, and 5.0ZI (1.91 ± 1.26) D and (0.92 ± 0.68) D (thinnest thickness t = 6.996, Mean K t = 2.554, Sim K t = 3.326, Sim A t = 2.324, CTI t = 3.116, 3.0ZI t = 2.686, 5.0ZI t = 3.768, P < 0.05), while no statistically significance in the Mean A between the MFS (1.11 ± 0.89) D and control group (0.99 ± 0.49) D (Mean A t = 1.898, P = 0.08); except for temple inferior, the significant decrease of pachymetry (including the center and the seven midperipheral locations) appeared in the MFS group compared with the control group. CONCLUSION: The characteristic of MFS in corneal topography is that corneal axial refractive power descends and corneal thickness decreases.
Assuntos
Córnea/patologia , Síndrome de Marfan/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
The phytoplankton assemblage of Zhubi Reef, a closed coral reef in Nansha Islands (South China Sea, SCS) was studied in June 2007. A total of 92 species belonging to 53 genera and four phyla have been identified. The dominant taxa in the lagoon were the diatom Chaetoceros and cyanobacteria Nostoc and Microcystis, while in reef flats were cyanobacteria Trichodesmium erythraeum, dinoflagellates Gymnodinium and Prorocentrum. The species richness and diversity were consistently lower in the lagoon than in reef flats. Classification and nMDS ordination also revealed significant dissimilarity in phytoplankton community structure between the reef flat and lagoon, with statistical difference in species composition and abundance between them (ANOSIM, p=0.025). Nutrient concentrations also spatially varied, with ammonium-enrichment in the lagoon, while high Si-concentration existed in reef flat areas. Both nutrient levels and currents in SCS may play important roles in determining the composition and distribution of microalgae in Zhubi Reef and SCS.
Assuntos
Recifes de Corais , Geografia , Espécies Introduzidas , Fitoplâncton/fisiologia , Água/química , Biomassa , Clorofila/análise , Clorofila/metabolismo , Clorofila A , Demografia , Ecossistema , Oceano Pacífico , Fitoplâncton/classificação , Fitoplâncton/metabolismoRESUMO
AIM: To evaluate the therapeutic efficacy of intracameral amphotericin B (ICAMB) injection in the treatment of keratomycosis. METHODS: The study design was a prospective controlled clinical trial. A total of 60 eyes of 60 patients were divided into two groups, 30 in the ICAMB injection group (group A) and 30 in the control group-topical application amphotericin B (group B). Serial measurements of the size of the keratomycosis-namely, two maximum linear dimensions perpendicular to each other, and the area and perimeter was done at start of therapy and follow up on day 3, 7, and 21. Rate of healing of the keratomycosis were measured as percentage decrease from the baseline parameter at each subsequent follow up. The data were analyzed by the non-parametric Wilcoxon rank sum test. RESULTS: The mean time to disappearance of hypopyon was 9.6±9.2 (range:1-26) days in group A and 26.8±20.8 (range:14-62) days in group B (P=0.03). The median percentage decrease in the size of the keratomycosis was significantly greater than that in the cord serum group at day 21(P<0.05) when measured in terms of the area and perimeter. A greater number of patients showed complete re-epithelialization in group A (n=27) than in group B (n=14) (P<0.05). None of the patients reported any side effects or discomfort with either treatment. CONCLUSION: ICAMB injection leads to faster healing of the keratomycosis refractory to all medical management and reducing time to disapperence of hypopyon compared to topical application amphotericin B.