scholarly journals Evaluation of C3435T MDR1 Gene Polymorphism in Adult Patient with Acute Lymphoblastic Leukemia

2011 ◽  
Vol 12 (1) ◽  
pp. 3-6
Author(s):  
Behnoosh Miladpoor ◽  
Alireza Tavassoli ◽  
Mohammad Hassan Meshkibaf ◽  
Fateme Kha
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Gene Polymorphism ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Mdr1 Gene ◽  
Healthy Controls ◽  
Chi Square ◽  
Glycoprotein P ◽  
Significant Difference ◽  
Mdr1 Polymorphism

Background: P-glycoprotein (P-gp) is a transmembrane pump encoded by MDR1 gene. It contributes in protection of the cells against xenobiotic and toxic compounds. P-gp also contributes in multidrug resistance in acute lymphoblastic leukemia (ALL). Human MDR1 polymorphism include C to T exchange at position 3435, individuals with TT polymorphism have lower expression of P-gp than the others with CC genotypes. Accumulation of xenobiotics in the cells can cause some diseases like cancers.Materials and Methods: To evaluate MDR1C3435T gene polymorphism in adult patients with ALL, 54 patients and 96 healthy controls were involved in our survey. Genotyping of ALL patients and healthy controls was performed by Polymerase Chain Reaction – Restriction Fragment- Length Polymorphism (PCR-RFLP). Data analysis was done by SPSS software through T-test and Chi- Square. Results: No significant difference was found between C3435T MDR1 gene polymorphisms and incidence of ALL in adult patients. Also there was not any significant difference between T and C alleles and incidence of ALL. Conclusion: C3435T MDR1 polymorphism is not associated with the incidence of ALL in the population studied. Keyword: P-gp; C3435T; MDR1; ALL; polymorphism DOI: 10.3329/jom.v12i1.5541J Medicine 2011; 12 : 3-6

scholarly journals Pancytopenia – (?) An obstacle in the diagnosis and outcome of pediatric acute lymphoblastic leukemia

2015 ◽  
Vol 04 (02) ◽  
pp. 068-071 ◽  
Author(s):  
Shruti Raja ◽  
Febe Renjitha Suman ◽  
Julius Xavier Scott ◽  
M. S. Latha ◽  
Aruna Rajenderan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cross Sectional Study ◽  
Control Group ◽  
Clinical Expertise ◽  
Chi Square ◽  
Cross Sectional ◽  
Significant Difference ◽  
Chi Square Test

Abstract Context: Acute lymphoblastic leukemia (ALL) ranks first among pediatric malignancies. 8-12% of ALL present with pancytopenia and 2% with hypocellular marrow a. Diagnosis of ALL in the background of pancytopenia and aplastic bone marrow is difficult. Aims: This study was aimed to compare the clinicopathologic, genetic, and outcome of paediatric ALL patients with and without pancytopenia. Settings and Design: This is a retrospective cross-sectional study. Susbjects and Methods: The study included all ALL patients presenting with pancytopenia. The control group included equal number of randomly selected patients with ALL without pancytopenia treated during the same period. Ethics committee approved this study. The demographic, laboratory, and treatment-related details were retrieved from the records and entered in an Excel sheet. Statistical Analysis Used: Data was analyzed with Chi-square test with IBM SPSS statistics 16 software. Results: Diagnosis by peripheral smear is significantly lower (P = 0.015) in comparison with the control group. There is no significant difference in diagnosis between the groups by bone marrow aspirate (P = 0.731) and biopsy (P = 0.849). The diagnosis of leukemia is misdiagnosed as hypo cellular/aplastic marrow in 10% of the pancytopenic patients. Flow cytometry yielded the diagnosis in all the pancytopenic patients. Though cytogenetic abnormalities are more common in pancytopenic group, it is not statistically significant (P = 0.106). There is no significant difference in treatment outcome between the groups (P = 0.0827%). Conclusions: Clinical expertise is highly essential to evaluate a case of pancytopenia to diagnose leukemia. Pancytopenia is an obstacle in the diagnosis of ALL without immunophenotyping. There is no significant difference in the outcome between the two groups.

scholarly journals Increased Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Acute Lymphoblastic Leukemia Survivors

2021 ◽  
Vol 10 (8) ◽  
pp. 1567
Author(s):  
Katarzyna Konończuk ◽  
Eryk Latoch ◽  
Beata Żelazowska-Rutkowska ◽  
Maryna Krawczuk-Rybak ◽  
Katarzyna Muszyńska-Rosłan
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Acute Lymphoblastic Leukemia ◽  
Binding Proteins ◽  
Lymphoblastic Leukemia ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Significant Difference

Childhood cancer survivors are highly exposed to the development of side effects after many years of cessation of anticancer treatment, including altered lipid metabolism that may result in an increased risk of overweight and metabolic syndrome. Adipocyte (A-FABP) and epidermal (E-FABP) fatty acid-binding proteins are expressed in adipocytes and are assumed to play an important role in the development of lipid disturbances leading to the onset of metabolic syndrome. The aim of this study was to investigate the association between serum A-FABP and E-FABP levels, overweight, and components of the metabolic syndrome in acute lymphoblastic leukemia survivors. Sixty-two acute lymphoblastic leukemia (ALL) survivors (34 females) were included in the study. The mean age at the time of the study was 12.41 ± 4.98 years (range 4.71–23.43). Serum levels of A-FABP and E-FABP were analyzed using a commercially available ELISA kit. The ALL survivors presented statistically higher A-FABP levels in comparison with the healthy controls (25.57 ± 14.46 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with body mass index (BMI) above the normal range (18 overweight, 10 obese) had a greater level of A-FABP compared to the ALL group with normal BMI (32.02 ± 17.10 vs. 20.33 ± 9.24 ng/mL, p = 0.006). Of all participants, 53.23% had at least one risk factor of metabolic syndrome; in this group, only the A-FABP level showed a statistically significant difference compared to the healthy control group (30.63 ± 15.91 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with two or more metabolic risk factors (16.13%) presented higher levels of both A-FABP (33.62 ± 17.16 vs. 15.13 ± 7.61 ng/mL, p = 0.001) and E-FABP (13.37 ± 3.62 vs. 10.12 ± 3.21 ng/mL, p = 0.021) compared to the controls. Univariable regression models showed significant associations between BMI and systolic blood pressure with the A-FABP level (coeff. 1.02 and 13.74, respectively; p < 0.05). In contrast, the E-FABP level was only affected by BMI (coeff. 0.48; p < 0.01). The findings reported herein suggest that the increased levels of A-FABP and E-FABP may be involved in the pathogenesis of overweight and the onset of metabolic syndrome in acute lymphoblastic leukemia. However, further longitudinal, prospective studies of fatty acid-binding proteins and their potential role in the pathogenesis of obesity and metabolic syndrome in ALL survivors remain to be performed.

scholarly journals Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Blast Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

The ABCs of Immunotherapy for Adult Patients With B-Cell Acute Lymphoblastic Leukemia

2017 ◽  
Vol 52 (3) ◽  
pp. 268-276 ◽  
Author(s):  
Troy Z. Horvat ◽  
Amanda N. Seddon ◽  
Adebayo Ogunniyi ◽  
Amber C. King ◽  
Larry W. Buie ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Data Extraction ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Efficacy And Safety ◽  
Car T Cells ◽  
Car T ◽  
American Society

Objective: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). Data Sources: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR). Study Selection/Data Extraction: Studies of pharmacology, clinical efficacy, and safety of rituximab, ofatumumab, obinutuzumab, inotuzumab, blinatumomab, and CAR T-cells in the treatment of adult patients with ALL were identified. Data Synthesis: Conventional chemotherapy has been the mainstay in the treatment of ALL, producing cure rates of approximately 90% in pediatrics, but it remains suboptimal in adult patients. As such, more effective consolidative modalities and novel therapies for relapsed/refractory disease are needed for adult patients with ALL. In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and CD19-targeted CAR T-cells have drastically changed the treatment landscape of B-cell ALL. Conclusion: Outcomes of patients with relapsed disease are improving thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells. Although the efficacy of these therapies is impressive, they are not without toxicity, both physical and financial. The optimal sequencing of these therapies still remains a question.

Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison

Blood ◽  
2009 ◽  
Vol 113 (6) ◽  
pp. 1375-1382 ◽  
Author(s):  
Jan J. Cornelissen ◽  
Bronno van der Holt ◽  
Gregor E. G. Verhoef ◽  
Mars B. van 't Veer ◽  
Marinus H. J. van Oers ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Donor Group ◽  
No Donor ◽  
Sibling Donor ◽  
Standard Risk

Abstract While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P < .001). Nonrelapse mortality estimated 16% (± 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P = .01). After risk-group analysis, improved outcome was more pronounced in standard-risk patients with a donor, who experienced an overall survival of 69% at 5 years (P = .05). In conclusion, standard-risk ALL patients with a sibling donor may show favorable survival following SCT, due to both a strong reduction of relapse and a modest nonrelapse mortality. This trial is registered with http://www.trialregister.nl under trial ID NTR228.

A prognostic scoring system for adult patients less than 60 years of age with acute lymphoblastic leukemia in first relapse

2009 ◽  
Vol 50 (7) ◽  
pp. 1126-1131 ◽  
Author(s):  
Anjali Advani ◽  
Tao Jin ◽  
Brian Bolwell ◽  
Edward Copelan ◽  
Mikkael Sekeres ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Scoring System ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
First Relapse

scholarly journals Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

Haematologica ◽  
2010 ◽  
Vol 95 (4) ◽  
pp. 589-596 ◽  
Author(s):  
A. Oriol ◽  
S. Vives ◽  
J. M. Hernandez-Rivas ◽  
M. Tormo ◽  
I. Heras ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Study Group

scholarly journals Effects of TPMT, NUDT15, and ITPA Genetic Variants on 6-Mercaptopurine Toxicity for Pediatric Patients With Acute Lymphoblastic Leukemia in Yunnan of China

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoyan Mao ◽  
Runxiu Yin ◽  
Gaoyuan Sun ◽  
Yan Zhou ◽  
Chunhui Yang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Yunnan Province ◽  
Medical Center ◽  
Lymphoblastic Leukemia ◽  
Free Survival ◽  
Ethnic Populations ◽  
Significant Difference ◽  
Pediatric All ◽  
Medical University ◽  
Tolerable Dose

Background: 6-Mercaptopurine (6-MP) is the cornerstone of current antileukemia regimen and contributes greatly to improve the survival of pediatric acute lymphoblastic leukemia (ALL) patients. However, 6-MP dose-related toxicities limit its application. TPMT, NUDT15, and ITPA are pharmacogenetic markers predicting 6-MP-related toxicities, but their genetic polymorphisms differ from those of ethnic populations. In Yunnan province, a multiethnic region of China, we had no genetic data to predict 6-MP toxicities. In this study, we evaluated the most common variants involved in 6-MP metabolism—TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) variants—in our cohort of pediatric ALL patients.Methods: A total of 149 pediatric ALL patients in the Affiliated Children's Hospital of Kunming Medical University (Yunnan Children's Medical Center) from 2017 to 2019 were enrolled in this retrospective study. We assessed the TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) frequencies and evaluated association between genotypes and 6-MP toxicities, 6-MP dose, and event-free survival (EFS) in these ALL patients.Results: The allele frequencies of TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) were 1.34%, 14.43%, and 18.79%, respectively. Only NUDT15 c.415C&gt;T (rs116855232) was strongly associated with 6-MP toxicity and 6-MP tolerable dose. NUDT15 c.415C&gt;T was related to leukopenia, p = 0.008, OR = 2.743 (95% CI: 1.305–5.768). The T allele was significantly correlated with 6-MP tolerable dose, dose of NUDT15 c.415C&gt;T wild genotype CC 39.80 ± 1.32 mg/m2, heterozygotes CT 35.20 ± 2.29 mg/m2, and homozygotes TT 18.95 ± 3.95 mg/m2. 6-MP tolerable dose between CC and TT had a significant difference, p = 0.009. Between CC and CT, and CT and TT, they had no significant difference. EFS showed no significant difference among NUDT15 c.415C&gt;T genotypes.Conclusion:NUDT15 c.415C&gt;T (rs116855232) was an optimal predictor for 6-MP toxicity and tolerable dose in pediatric ALL patients from Yunnan province, a multiethnic region in China, and would play an important role in precise therapy for ALL.

Sign in / Sign up

Export Citation Format

Share Document