bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Parvovirus B19 and Herpesvirus-6 Serology in Brazilian Children with Common B Cell Precursor Acute Lymphoblastic Leukemia
Authors: Silva Fernanda A , Vasconcelos Gisele M , Cordeiro Synara NS , Sant’Ana Mariana , de Carvalho Silvia Maia Farias , Pombo-de-Oliveira Maria S. 
Published: April 2020

Abstract
Background. Indirect epidemiologic evidences have suggested that viral infections may represent an important risk factor in the etiological mechanisms of B cell precursor lymphoblastic leukemia (BpALL), specially common-ALL. Parvovirus B19 (PvB19) is associated with aplastic crisis, thrombocytopenia, and congenital anemia. Five studies have reported the concurrent PvB19 infection in pediatric ALL. In a view of the increasing contest about the direct or indirect role of viral infection in ALL, we evaluated the possible associations of PvB19 and herpes virus 6 (HHV-6) in samples from children suffering from hematological disorders in order to estimate the magnitude of risk of association with common-BpALL.
Material and Methods. A total of 659 blood samples were randomly selected to perform the serological tests. They were part of diagnostic samples referred to CPq-INCA-Rio de Janeiro, Brazil, from 2002–2006, for diagnostic purpose. Blood samples were exclusively selected from patients in whom samples were taken at the time of the onset of sickness. The diagnosis of BpALL was based on immunophenotyping methods according to EGIL criteria. The presence of serum antibodies for PvB19 and HHV-6 were determinate by enzyme-linked immunosorbent assay. Statistical analyses were conducted using SPSS for Windows 11.0. All p values were two sided; p&lt;0.05 was considered statistically significant.
Results. Common-ALL (n=176) and non-leukemic samples (n=107) considered as control group were stratified according to age-groups at diagnosis. Age distribution was:
less than 2 years (15.5%); 2–6 years-old (46.0%), and 7–12 years-old (17.7%).
The estimation of associated risk PvB19 IgG+ antibodies with common-BpALL was OR 0.53 95% CI (0.52–0.54); whereas HHV-6 IgG was OR 2.36, 95% CI (1.08–5.17).
Conclusions. We find out a higher prevalence of HHV-6 antibodies in patients with common-BpALL, suggesting an association between HHV-6 infection e common-BpALL in Brazilian children. There is a long history in developed countries regarding the role of infections in leukemogenesis process. Further tests are necessary to confirm these results.
Environmental and Socioeconomic Factors in Children with Acute Lymphoblastic Leukemia
Authors: Timur Cetin , Yilmaz Oznur , Yoruk Asim , Erguven Muferet , Imdadoglu Timucin , Kavakli Kaan 
Published: April 2020

Abstract
In our study, we aimed to evaluate environmental and socio-economic conditions in children with Acute Lymphoblastic Leukemia (ALL) and to point at possible etiologic factors that can affect leukemia risk. The parents of 105 children diagnosed and treated as ALL between the years 1997 –2007 in our clinic of Pediatric Hematology-Oncology were questioned in terms of environmental and socio-economical factors and results were compared with control group that consisted of 102 healthy children with similar age and gender. Educational level and monthly income were similar between the groups. Occupational exposure of fathers to dust and chemicals were significantly higher in leukemia group (OR:2.00; %95 CI=1.41–3.50, p:0.015). Living near transformer stations (OR: 4.08; %95 CI= 1.3–12.76, p: 0.034) and high-voltage power lines (OR: 2.43; %95 CI= 1.05–5.63, p:0.01) is found to be associated with increased risk of leukemia in children. There was no significant difference in terms of living near base stations (p&gt;0.05). Exposure to industrial air pollution was significantly higher in leukemia group and was related to an elevated risk of ALL (OR: 26.77; %95 CI= 3.53–202.80, p:0.001). There was no significant difference in terms of exposure to insecticides and pesticides between the groups (p:&gt;0.05). In conclusion, leukemia is a disease with multi-factorial etiology that occurs as a result of interactions of genes and environment. The list of possible chemical, physical and biologic agents suspected to play a role in its etiology increase with developing technology and environmental pollution. However there are no sufficient data and more extended studies have to be carried out.
Histone Deacetylase Inhibition Improves Differentiation of Dendritic Cells from Leukemic Blasts of Patients with TEL/AML1-Positive Acute Lymphoblastic Leukemia
Authors: Schmidt Kerstin , Seeger Karl , Scheibenbogen Carmen , Bender Roderich , Süßmilch Sina , Salama Abdulgabar , Moldenhauer Anja 
Published: April 2020

Abstract
Histone deacetylase inhibitors (HdI) could potentially improve the differentiation of leukemic dendritic cells (DC). Therefore, 100 bone marrow samples from patients with acute lymphoblastic leukemia (ALL) were cultured in the presence of TNFα, GM-CSF, c-kit ligand and FLT3 ligand with or without interleukin-3 and –4, and after administration of the HdI valproic acid (VAL), suberoylanilide hydroxamic acid (SAHA), isobutyramid or trichostatin A. Twenty-six of these ALL samples were positive for the t(12;21) translocation encoding the fusion gene TEL/AML1. SAHA increased CD83 expression of TEL/AML1- positive blasts in conditions without interleukins (36±6.5% versus 26.3±7.1%, p&lt; 0.05), while SAHA and VAL increased the number of CD86(+)80(−) cells in the presence of interleukins (12.5±2.8 ×104 versus 6.3±1.1 ×104 cells). VAL and isobutyramid supported the allostimulatory capacities of TEL/AML1-positive leukemic DC (48.5±6.4 ×103cpm and 50.3±7.1 ×103cpm) and reduced those of TEL/AML1-negative DC (41.8±6.8 ×103 cpm versus 52.8±11.2 ×103cpm, p= 0.05). Cytotoxic T-cells sensitized with leukemic DC produced more INFγ and TNFα upon presentation of the TEL/AML1 peptide. They also induced the cytotoxic lysis of non-differentiated blasts, which was enhanced when TEL/AML1-positive DC had developed after addition of VAL or SAHA. In conclusion, the use of HdI in the differentiation of leukemic DC from patients with TEL/AML1-positive ALL is recommended.
Adults with Acute Lymphoblastic Leukemia and T(1;19) Abnormality Have a Favorable Outcome with Hyper-CVAD Chemotherapy
Authors: Garg Ravin Jain , Kantarjian Hagop M , Thomas D. A , Faderl Stefan , Ravandi Farhad , Lovshe Denise , Pierce Sherry , O’Brien Susan 
Published: April 2020

Abstract
Among the well-described cytogenetic abnormalities in adults with acute lymphoblastic leukemia (ALL), a translocation involving chromosomes 1 and 19 [t(1;19) (q23;p13)] occurs in a small subset but has varyingly been associated with a good or bad prognosis in different studies.
Adults with ALL and t(1;19) treated at M.D. Anderson Cancer Center were reviewed. Their clinical features and outcome were compared to those with other cytogenetic abnormalities. Endpoints included complete remission rate (CR), complete response duration (CRD) and overall survival (OS).
Of 411 adults with pre-BALL, 12 patients had t(1;19). Ten of the 12 patients with t(1;19) received Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, Dexamethasone alternating with Methotrexate and high-dose Cytarabine); the other 2 were treated with VAD (Vincristine, Adriamycin, Dexamethasone). All 12 patients achieved CR; the 3-year survival rate was 73%. Patients with t(1;19) had significantly better CRD and OS when compared to all other patients combined as well as individually to patients with Ph+, t(4;11), and lymphoma-like abnormalities [6q(−), 14q+, t(11;14), t(14;18)].
Adults with ALL and t(1;19) have an excellent prognosis when treated with the Hyper-CVAD regimen.
Outcome of patients by cytogenetic group: t(1;19) vs. individual cytogenetic groups
OVERALL SURVIVAL N Fail 3-Year % Median (weeks) P-value T(1,19) 12 3 73 Not recorded Diploid 138 72 52 179 0.09 Lymphoma-like 20 17 35 54 0.008 Ph+ 117 88 23 68 0.0002 Miscellaneous 112 56 56 236 0.17 T(4,11) 12 10 0 58 0.002 COMPLETE RESPONSE DURATION (CRD) N Fail 3-Year % Median (weeks) P-value T(1,19) 12 2 80 Not recorded Diploid 133 59 54 177 0.06 Lymphoma-like 16 13 34 89 0.009 Ph+ 102 52 42 63 0.006 Miscellaneous 100 41 59 401 0.16 T(4,11) 11 7 NR 45 0.018
NOD/SCID/γcnull mice provide a Unique Model to Investigate Childhood Haematopoietic Malignancies
Authors: Kato Itaru , Niwa Akira , Umeda Katsutsugu , Ito Mamoru , Heike Toshio , Nakahata Tatsutoshi 
Published: April 2020

Abstract
Remarkable improvements in the outcome for childhood haematopoietic malignancies have been made during the past few decades. However, haematopoietic malignancies are the most common pediatric malignancy, and outcome after relapse is generally poor. Recent reports suggest that at least some cases of human leukemia and cancer are arranged in a hierarchical fashion and maintained by rare “tumor-propagating cells”. However, whether the malignant clone arises from such a leukemic stem cell fraction has not been clarified in most haematopoietic malignancies other than acute myelogenous leukemia (AML). Establishment of an assay capable of generating of childhood haematopoietic malignancies from patient oriented blast cells will provide new insight into the haematopoietic malignancies biology and the mechanism of the development of haematopoietic malignancies in vivo. The recently described highly immunodeficient NOD/SCID/gamma null (NOG) mice provide a number of advantages. This strain, with life expectancy more than 90 weeks, is more robust than strains such as NOD/SCID and support generation of haematopoietic malignancies from transplanted human blast cells. In the present study, childhood haematopoietic malignancies cells, such as acute lymphoblastic leukemia(ALL; n=7), AML (n=4), juvenile myelomonocytic leukemia(JMML; n=1), Lymphoma(n=1), and Transient Myeloproliferative Disorder(n=1), are transplanted into 2.4Gy irradiated or non-irradiated NOG mice. The transplanted mice have splenomegaly, hepatomegaly, nephromegaly and testicular enlargement and developed haematopoietic malignancies which is the same flow cytometric immunophenotype and pathological pattern of the patient from 4 weeks after intravenous injection of 5×102-1×108 blast cells. The transplanted mice can live as long as 24 weeks after transplantation with more than 95% blasts in the bone marrow. The blast cells harvested from the bone marrow and the spleen generated the haematopoietic malignancies in tertiary transplantation especially in ALL. We report here examination results of reconstituted childhood haematopoietic malignancies in NOD/SCID/gamma null mice after the transplantation of patient oriented blast cells.
Outcome of Adults with Acute Lymphocytic Leukemia (ALL) with Second Salvage Therapy
Authors: O’Brien Susan , Thomas Deborah , Ravandi-Kashani Farhad , Faderl Stefan , Cortes Jorge , Borthakur Gautam , Pierce Sherry , Manero Guillermo Garcia- , Kantarjian Hagop 
Published: April 2020

Abstract
Background and Aims. The outcome of adults with ALL undergoing second salvage therapy is poorly characterized. The aim of this study was to determine the outcome and prognostic factors associated with second salvage therapy in patients with ALL.
Study Group and Methods. A total of 288 patients treated for ALL in second salvage at our institution were analyzed.
Results. 53 patients (18%) achieved complete remission (CR). The median remission duration was 7 months. The median survival was 3 months. By multivariate analysis, prognostic factors independently associated with achievement of CR were: duration of first CR, and platelet count. Patients with a first CR &lt; 36 months and a platelet count &lt; 50 × 109/L had an expected CR rate of 7%. By multivariate analysis, prognostic factors independently associated with survival were: duration of first CR, percent of marrow blasts, platelet count, and albumin levels. Expected 12-month survival rates for patients with 0–1, 2, 3, or 4 adverse factors were 33%, 14%, 8%, and 0%, respectively. A repeat multivariate analysis using landmark assessment at 6 weeks selected achievement of CR as adding significantly to the survival benefit (p = 0.0001, hazard ratio 0.51). Only 22 patients (8%) were able to undergo allogeneic stem cell transplant as second salvage therapy; their one-year survival rate was 18%.
Conclusions. The outcome of adults with ALL undergoing second salvage therapy is poor. Novel effective therapies against ALL are needed in this subset of patients.
Resveratrol Inhibits Proliferation and Induces Apoptosis of Mouse Pten Null T-Cell Acute Lymphocytic Leukemia Cells
Authors: Liu Qing , Gao Xiuhua , Yin Cheng C. , Ling Chen , You M. James 
Published: April 2020

Abstract
Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a plant antibiotic produced in a wide variety of plants (including grapes, peanuts, and mulberries) in response to stress, injury, UV irradiation, and fungal infection, has been shown to inhibit cell growth of several types of cancer. Here, we have investigated the effects of Resveratrol on the proliferation and apoptosis in T-cell lymphocytic leukemia (T-ALL) cells. These T-ALL cells were derived from T-ALL of mice with the T-cell specific deletion of the Pten tumor suppressor gene. Flow cytometric analysis demonstrated that the T-ALL cells are positive for CD4 and negative for CD8. Morphologically, the T-ALL cells strikingly mimic human counterparts. Western blot analysis confirmed the absence of Pten expression and high expression level of phosphorylated Akt of the T-ALL cells. A single dose treatment of the T-ALL cells with Resveratrol (ranging from 3 to 50 mM) resulted in significant decrease in cell growth. In addition, Resveratrol treatment with the above concentrations showed a remarkable increase in apoptosis. The vehicle treated T-ALL cells grew exponentially and had minimal apoptotic cell death. Further investigation of the mechanisms of the Resveratrol’s efforts on inhibiting T-ALL cell growth and inducing apoptosis is on-going. In addition, combination of Resveratrol with conventional chemotherapy reagents for treating T-ALL is also being evaluated.
Prognosticating of Relapse Risk Based on Multiparameter Flow Cytomeric Assessment of Minimal Residual Disease in Patients with Acute Myeloid Leukemia
Authors: Wan Suigui , Qiu Lugui , Sun Xuejing , Zhao Hong , Su Li , Xu Juan 
Published: April 2020

Abstract
Abstract Objective: To investigate the prognosticating of relapse risk based on assessment of minimal residual disease(MRD) in patients with acute myeloid leukemia(AML).
Methods: Multiparameter flow cytometry (MPFC) analysis were used to detect the leukemia-associated aberrant immunophenotype (LAIP)of the pretreated patients with AML and assess the level of MRD after remission induction(Post-Ind MRD) and consolidation therapy(Post-Cons MRD).
Results: The results showed that definite LAIP could be detected in about 94.3%of patients (115/122) with AML (except APL). Only one LAIP was identified in 15 cases (13.0%), but in other 100 cases (87.0%), two or more LAIP were identified. The most frequent LAIP identified was cross-lineage antigen expression (40.9%). The percentages of asynchronous antigen expression, antigen over-expression and antigen lack expression were 20.9%, 27.0% and 34.8% respectively. MRD frequency was monitored in 41 CR patients with AML after remission induction chemotherapy and 2 or more cycles of consolidation chemotherapy. 24 patients were Post-Ind MRD+ and 17 patients were Post-Ind MRD−. The percentages of relapse in Post- Ind MRD+ and Post-Ind MRD− were 75.0%(18/24) and 29.4%(5/17) respectively after consolidation chemotherapy. The relapsed free survival(RFS) of the patients with Post-Ind MRD+ and Post-Ind MRD− was 49.06±6.53 months and 11.92±1.64 months(P&lt;0.0001) respectively. 18 patients were Post-Cons MRD+ and 23 patients were Post-Cons MRD−. The percentages of relapse in Post-Cons MRD+ and Post-Cons MRD− patients were 100%(18/18) and 21.7%(5/23) respectively after consolidation chemotherapy. The RFS of the patients with Post-Cons MRD+ and Post-Cons MRD− was 41.74±5.52 months and 10.06±1.72 months (P&lt;0.0001) respectively.
Conclusions: The level of post-Ind MRD and post-Cons MRD identified in the patients with AML was highly associated with their RFS. MRD measured by MPFC provided prognostic information in AML patients.
Polymorphisms in Myeloid Cell Leukemia-1 and the Risk for Acute Myeloid Leukemia
Authors: Kim Hee Nam , Yu Li , Kim Nan young , Lee Il-Kwon , Kim Yeo-Kyeoung , Yang Deok-Hwan , Lee Je-Jung , Kim Hee-je , Min Woo-Sung , Park Moo-Rim , Jo Deog-Yeon , Won Jong-Ho , Kwak Jae-Yong , Kim Hyeoung- Joon 
Published: April 2020

Abstract
The essential pathogenic mechanism in acute myeloid leukemia (AML) is a heterogeneous group of malignant diseases arising as the result of progressive genetic damage occurring in hemopoietic progenitor cells. Mcl-1 (myeloid cell leukemia-1), an antiapoptotic protein of the Bcl-2 family, is located on chromosome 1 and has three exons and two introns. Overexpression of Mcl-1 delays apoptosis induced by cytotoxic agents, c-myc overexpression, and growth factor withdrawal in hematopoietuc cells. To evaluate the association between genetic variants of Mcl-1 gene and risk of AML, we genotyped two polymorphisms in promoter of Mcl-1[rs3738484; −324 C&gt;A and rs3831987; −284 insertion(6bp or18bp)/deletion]. A case-control study of 728 controls and 660 cases was conducted in Chonnam National University Hwasun Hospital, Korea. The Mcl −324 CA and combined CA/AA genotype was significantly associated with a decreased risk for AML [odds ratio (OR) CA = 0.75; 95% confidence interval (CI) = 0.60–0.95; ORCA/AA = 0.76; 95% CI = 0.61–0.96]. There was no association with the Mcl -284 insertion/deletion and AML. The haplotype A-ins18bp is significantly associated with the risk of AML. Using subjects with the haplotype A- del, the OR of haplotype A-ins18bp is 5.87 (95% CI 1.7–20.06 p= 0.006). Our results suggest that antiapoptotic protein, Mcl-1 polymorphism may influence susceptibility to AML.
Expression and Prognostic Significance of MDR and IAP-Family Genes in Patients with Acute Myeloid Leukemia
Authors: Cioch Maria B. , Kocki Janusz , Kotwica Katarzyna , Gromek Tomasz , Dmoszynska Anna 
Published: April 2020

Abstract
Introduction. Refractory Acute Myeloid Leukemia (AML) is associated with very bad prognosis. One of the major reason of induction chemotherapy failure is the expression of genes and proteins responsible for multidrug resistance (Multidrug Resistance 1 - MDR1, Multidrug Resistance-Related Protein 1 - MRP1, Breast Cancer Resistance Protein-BCRP, Lung Cancer Related Protein - LRP) and apoptosis (IAP-family genes: XIAP, cIAP1, cIAP2, survivin). The aim of the study was the evaluation of the influence of MDR and IAP-family genes expression on results of chemotherapy in patients (pts) with AML.
Material and methods. The study was performed in 45 pts (20 females and 25 males; ranged from 18 to 82 years - mean 51.2) with newly diagnosed AML. There were following types acc. FAB classification: M0–1, M1–5, M2–13, M3–4, M4–16, M5–6 and cytogenetic risk groups: favorable-8, intermediate-29 and unfavorable-8 pts. The genes expression in leukemic cells was detected by RT-PCR method. All pts were treated with induction and consolidation therapy acc. Polish Adult Leukemia Group (PALG).
Results. The expression of MDR1 gene was detected in 47%, MRP1 in 21%, BCRP in 10%, LRP in 26% and IAP-family genes in 78% of pts. Expression of MDR1 was significantly higher in M5 (p=0.02), but expression of cIAP1 and cIAP2 in M4 type (p=0.01). There was significant difference in MDR1 expression between unfavorable and good risk cytogenetic group (p=0.03), but there was none difference between cytogenetic groups in expression of IAP-family genes. There was significant difference in MDR1 expression between pts who achieved complete remission (CR) and pts without CR (p=0.01). When the expression of MDR1 gene was associated with the expression of BCRP and LRP, CR was never obtained. In all pts with complex genetic changes (MDR1+MRP1, MDR1+BCRP+LRP, MDR1+MRP1+BCRP+LRP) CR after one course of induction chemoterapy was not obtained. There was significant difference between CR rate after one course of chemotherapy in pts without MDR genes expression or expression only one gene and in pts with expression of two or more genes (p=0.02). There was no correlation between IAP-family genes expression and CR rate. Despite of differences in post-consolidation therapy (bone marrow transplantation in some pts) expression of MDR1 and survivin genes correlated with overall surival rate (p=0.05 and 0.03, respectively).
Conclusions. Results of our studies on expression of MDR and IAP-family genes in pts with AML showed that expression of MDR genes better predicted response on induction chemotherapy than IAP genes. After confirmation on larger group of pts these findings may have important significance in defining of prognosis in AML and individualization of induction and postremission therapy, eventually with new generation of MDR modulators.
Apoptosis Was Induced by Casticin in Acute Myelocytic Leukemia Cells
Authors: Jin Jie , Shen Jia-Kun , Du Hua-ping , Yang Min , Wang Yun-Gui 
Published: April 2020

Abstract
Casticin, a component from Vitex rotundifolia wich was widely used as an anti-inflammatory agent in Chinese traditional medicine, was reported to have anti-tumor activities in lung cancer and breast cancer. There are yet no reports on roles against acute myelocytic leukemia (AML). This study aims to elucidate the anti-leukemic activity of casticin on AML cells. We investigated the efficient efficacy and the mechanisms by which casticin triggers cell death in AML cells by analyzing cell cycle perturbations, apoptosis-related marker expression. Cell viability was measured by MTT method; apoptosis and cell cycle arrest were determined by flow cytometry and AV-PI assay. Western blot was performed to measure the apoptosis-related marker. Concentration-dependant cell deaths were observed in AML cell lines including K562, U937 and THP-1, with IC50 values of 24h (hours) being 47.4μM, 67.8μM and 61.7μM, respectively. Time-dependant cell deaths were also observed. At the concentration of 20μM casticin, 45.7%, 76.1% and 80.9% of K562 cells were inhibited at 24h, 48h and 72h, respectively; 24.7%, 30% and 61% of U937 cells were inhibited at 24h, 48h and 72h, respectively; while for THP-1, 29%, 41.8% and 53.9% were inhibited at 24h, 48h and 72h, respectively. Apoptosis was found using AV-PI staining by flow cytometry analysis. We observed an obvious G2/M phase increase prolongation in casticin treated K562 cells. BThe distribitions of G2/M phase were 2.9%, 33.6%, 75.3%, 54.9%, 29.7% and 27.0% in K562 cells after treated by 20μM casticin for 0h, 6h, 12h, 24h, 36h and 48h, respectively. Furthermore, apoptosis-related proteins, PARP and caspase 3, were cleaved in casticin treated K562 cells. Taken together, these results demonstrated that casticin can induce leukemic cell death through apoptosis, suggesting that casticin could be a promising therapeutic agent against acute myeloid leukemia.