scholarly journals Detection of Methylene Tetrahydrofolate Reductase Gene Polymorphism (C677T) In Sudanese Patients with Chronic Myeloid Leukemia

2019 ◽  
Vol 9 (6) ◽  
pp. 162-168
Author(s):  
Negood Abdelhameed Osman ◽  
Alsadig Gassoum ◽  
Sanabel Alhussien Ahmed ◽  
Nihad Elsadig Babiker

Chronic myeloid leukaemia (CML) is a kind of cancer that affects the white blood cells and resort to progress slowly through many years. It’s occur at any age, but is most common in older (60-65 years) of age. This is a cross sectional study aimed to detect MTHFR gene polymorphism (C677T) among Sudanese patients diagnosed with Chronic Myeloid Leukaemia and conducted at the research laboratory of the national center of neurological sciences (NCNS), Khartoum, Sudan.50 patients with Chronic Myeloid Leukemia (CML) diagnosed as BCR-ABL positive by RT-PCR used as a cases and 50 apparently healthy individuals as a control. A 5 ml of blood samples were collected in EDTA anticoagulant container for DNA Extraction and white blood cells count, hemoglobin level and platelets count. Genotyping of the MTHFR was carried out using PCR technique and the SNP (C677T) confirmed by sequencing a subset of samples. The results were analyzed using bioinformatics tools. The results showed; the most affected age group in the patients was 51-60 years followed by 41-50 years which constituted 32% and 30%, respectively. The hematological findings revealed that, the mean of TWBCs was 47.4, HB was 11.9 for patients, 7.2 and 14.1 respectively for control group (P = 0.000). PLT was 313.5 for patients and 287.5 for control group (P = 0.187). MTHFR gene was detected in the all patients (198pb) by the PCR, Sequence results were aligned with the reference sequence of MTHFR gene, the polymorphic C >T was found to be matched with the registered mutation in NCBI data base. This study provides the first evidence for associations of MTHFR gene polymorphism with the risk of chronic myeloid leukemia in Sudanese patients. The C >T genotype of the rs 677 polymorphism in MTHFR gene may have a promoting effect on chronic myeloid leukemia. Keywords: Chronic myeloid leukaemia (CML), DNA, PCR, RT-PCR, MTHFR

2012 ◽  
Vol 33 (2) ◽  
pp. 85-89 ◽  
Author(s):  
Ali Yasar ◽  
Kamer Gunduz ◽  
Ece Onur ◽  
Mehmet Calkan

The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.


2019 ◽  
Vol 51 (1-2) ◽  
pp. 40-43
Author(s):  
Md Mokter Hossain ◽  
Mollah Obayedullah Baki ◽  
Tamanna E Nur ◽  
Zannatul Ferdous Jesmin

Background: First generation tyrosine kinase inhibitor, imatinib revolutionized the treatment of chronic myeloid leukaemia, and is now the front line therapy. Imatinib provides substantial cytogenetic and molecular remission, with minimal normal hematopoiesis suppression or side effects and is now first line therapy. Objective: The aim of this prospective study was to determine the efficacy of imatinib therapy in the management of chronic myeloid leukemia in Bangladesh. Methods: This prospective study was done from June 2012 to May 2018. In this period we treated eight chronic myeloid leukaemia patients with imatinib, in Khulna division, Bangladesh. Results: Majority of the patients (50%) were in the age group of 21-30 years. Three patients died as because those patients were too poor to continue drugs. Another 5 patients were in good health and continuing follow up monthly. Among five patients, one patient have two healthy son. Conclusion: Imatinib therapy is an effective treatment regimen in the management of chronic myeloid leukaemia. The best result can be obtained if CML is dignosed earlier. Bang Med J (Khulna) 2018; 51 : 40-43


2013 ◽  
Vol 3 (2) ◽  
pp. 113-115
Author(s):  
Tareq Mahmud Bhuian ◽  
Md. Mahbubur Rahman ◽  
Md. Nazmul Hoque ◽  
Muhammad Abdur Rahim ◽  
Md. Motiur Rahman ◽  
...  

Tuberculosis (TB) may complicate patients with chronic myeloid leukaemia (CML) receiving imatinib mesylate, but concomitant diagnosis of TB and CML is rare. Here, we present a middle aged Bangladeshi diabetic lady who got admitted because of prolonged pyrexia, ascites and splenomegaly. Diagnostic workup confirmed peritoneal TB and CML. Being an uncommon entity, we are reporting the case. Birdem Med J 2013; 3(2): 113-115 DOI: http://dx.doi.org/10.3329/birdem.v3i2.17217


2008 ◽  
Vol 52 (8) ◽  
pp. 1374-1381 ◽  
Author(s):  
Kelly Cristina de Oliveira ◽  
Bianca Bianco ◽  
Ieda T. N. Verreschi ◽  
Alexis Dourado Guedes ◽  
Bianca Borsato Galera ◽  
...  

BACKGROUND: Dysfunctions in the folate metabolism can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of this enzyme (C677T and A1298C) reduce its activity, but when associated with aneuploidy studies the results are conflicting. The objective of the present study is to analyze the MTHFR gene polymorphisms in women with Turner Syndrome and in a control group, correlating the findings to the chromosomal aneuploidy. METHODS: The study comprised 140 patients with Turner Syndrome, of which 36 with chromosome mosaicism and 104 non-mosaics, and a control group of 209 fertile and healthy women without a history of any offspring with aneuploidy. Polymorphisms C677T and A1298C were studied by RFLP-PCR and the results were statistically analyzed. RESULTS: The frequency of genotypes MTHFR 677CC, 677CT and 677TT in the patients with Turner Syndrome and chromosome mosaicism was, respectively, 58.3%, 38.9% and 2.8%. Among the patients with non-mosaic Turner Syndrome, 47.1% presented genotype 677CC, 45.2% genotype 677CT, and 7.7% genotype 677TT. Among the 209 individuals of the control group, genotypes 677CC, 677CT and 677TT were found at the following frequencies: 48.3%, 42.1% and 9.6%, respectively. As for polymorphism A1298C, the patients with Turner Syndrome and chromosome mosaicism presented genotypes 1298AA, 1298AC and 1298CC at the following frequencies: 58.3%, 27.8% and 13.9%, respectively. Among the non-mosaic Turner Syndrome patients, genotype 1298AA was found in 36.5%, genotype 1298AC in 39.4%, and genotype 1298CC in 22.1%. In the control group, genotypes 1298AA, 1298AC and 1298CC were present at the following frequencies: 52.6%, 40.7% and 6.7%, respectively. CONCLUSION: No correlation was observed between the MTHFR gene polymorphism 677 and chromosomal aneuploidy in the Turner Syndrome patients. However, the MTHFR gene polymorphism at position 1298, mainly genotype 1298CC that reduces the enzyme efficiency, was more frequent in the group of Turner Syndrome patients, suggesting its involvement in mechanisms related to chromosomal imbalances.


Tumor Biology ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. 8913-8919 ◽  
Author(s):  
Song Dong ◽  
Yueling Liu ◽  
Jieping Chen

2006 ◽  
Vol 2 (4) ◽  
pp. 467-476 ◽  
Author(s):  
Bentham Science Publisher Bentham Science Publisher

Author(s):  
Sezgi Kipcak ◽  
Buket Ozel ◽  
Cigir B. Avci ◽  
Leila S. Takanlou ◽  
Maryam S. Takanlou ◽  
...  

Background: Chronic myeloid leukemia (CML), is characterized by a reciprocal translocation t(9;22) and forms the BCR/ABL1 fusion gene, which is called the Philadelphia chromosome. The therapeutic targets for CML patients which are mediated with BCR/ABL1 oncogenic are tyrosine kinase inhibitors such as imatinib, dasatinib, and nilotinib. The latter two of which have been approved for the treatment of imatinib-resistant or intolerance CML patients. Mitotic catastrophe (MC) is one of the non-apoptotic mechanisms which frequently initiated in types of cancer cells in response to anti-cancer therapies; pharmacological inhibitors of G2 checkpoint members or genetic suppression of PLK1, PLK2, ATR, ATM, CHK1, and CHK2 can trigger DNA-damage-stimulated mitotic catastrophe. PLK1, AURKA/B anomalously expressed in CML cells, that phosphorylation and activation of PLK1 occur by AURKB at centromeres and kinetochores. Objective: The purpose of this study was to investigate the effect of dasatinib on the expression of genes in MC and apoptosis pathways in K562 cells. Methods: Total RNA was isolated from K-562 cells treated with the IC50 value of dasatinib and untreated cells as a control group. The expression of MC and apoptosis-related genes were analyzed by the qRT-PCR system. Results: The array-data demonstrated that dasatinib-treated K562 cells significantly caused the decrease of several genes (AURKA, AURKB, PLK, CHEK1, MYC, XPC, BCL2, and XRCC2). Conclusion: The evidence supply a basis to support clinical researches for the suppression of oncogenes such as PLKs with AURKs in the treatment of types of cancer especially chronic myeloid leukemia.


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Shiman Zuo ◽  
Luchen Sun ◽  
Yuxin Wang ◽  
Bing Chen ◽  
Jingyue Wang ◽  
...  

AbstractChronic myeloid leukemia (CML) is characterized by the accumulation of malignant and immature white blood cells which spread to the peripheral blood and other tissues/organs. Despite the fact that current tyrosine kinase inhibitors (TKIs) are capable of achieving the complete remission by reducing the tumor burden, severe adverse effects often occur in CML patients treated with TKIs. The differentiation therapy exhibits therapeutic potential to improve cure rates in leukemia, as evidenced by the striking success of all-trans-retinoic acid in acute promyelocytic leukemia treatment. However, there is still a lack of efficient differentiation therapy strategy in CML. Here we showed that MPL, which encodes the thrombopoietin receptor driving the development of hematopoietic stem/progenitor cells, decreased along with the progression of CML. We first elucidated that MPL signaling blockade impeded the megakaryocytic differentiation and contributed to the progression of CML. While allogeneic human umbilical cord-derived mesenchymal stem cells (UC-MSCs) treatment efficiently promoted megakaryocytic lineage differentiation of CML cells through restoring the MPL expression and activating MPL signaling. UC-MSCs in combination with eltrombopag, a non-peptide MPL agonist, further activated JAK/STAT and MAPK signaling pathways through MPL and exerted a synergetic effect on enhancing CML cell differentiation. The established combinational treatment not only markedly reduced the CML burden but also significantly eliminated CML cells in a xenograft CML model. We provided a new molecular insight of thrombopoietin (TPO) and MPL signaling in MSCs-mediated megakaryocytic differentiation of CML cells. Furthermore, a novel anti-CML treatment regimen that uses the combination of UC-MSCs and eltrombopag shows therapeutic potential to overcome the differentiation blockade in CML.


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