The association between FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a among chronic granulocytic leukemia patients treated with imatinib mesylate

Background: The gene FOXO3a has been elucidated to govern the development of chronic granulocytic leukemia (CGL). Moreover, it has been suggested that the levels of FOXO3a in circulation are affected by the FOXO3a rs4946936 gene polymorphism. However, no study has assessed the correlation between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. The objective of this study was to assess the association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a in CGL patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted from February 2019 to February 2020. The genotyping of FOXO3a rs4946936 gene polymorphism was conducted using PCR-RFLP, and the levels of FOXO3a were assessed using ELISA. The association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a were assessed using multiple logistic regression. Results: A total of 60 CGL patients were assessed in our study. Among them, the CC, CT, and TT genotypes of the FOXO3a rs4946936 gene polymorphism were 35.0%, 48.3%, and 16.7% respectively. Our calculation revealed that elevated levels of FOXO3a were found in CGL patients with the CC genotype of the FOXO3a rs4946936 gene polymorphism. While we failed to clarify the association between either the CT or the TT genotype of FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. Conclusion: Our study identifies that the CC genotype of the FOXO3a rs4946936 gene polymorphism affects the elevated levels of FOXO3a in CGL patients treated with imatinib mesylate.

Effect of Granulocyte Colony-Stimulating Factor Combined with Erythropoietin on Chronic Granulocytic Leukemia with Anemia and Its Effect on Nutritional Status

Objective: To investigate the clinical effect of granulocyte colony-stimulating factor combined with erythropoietin on chronic granulocytic leukemia with anemia and its effect on nutritional status. Methods: 60 patients of chronic granulocytic leukemia of our hospital with anemia induced by maintenance chemotherapy were randomly divided into two groups. Patients in the control group received routine treatment, while patients in the observation group received basal treatment with granulocyte colony-stimulating factor and erythropoietin. The nutritional status before and after treatment as well as the immune function and the incidence of blood transfusion and adverse events were compared between the two groups. Results: There was no significant difference in hemoglobin, hematocrit, nutritional status and immune function between the two groups before treatment (P>0.05). Those after treatment were significantly higher than that before treatment (P<0.05). After treatment, the percentage of CD4* cells in the control group was significantly higher than that before treatment (P<0.05), but the percentage of CD8* cells and CD47/CD8* cells did not change significantly (P>0.05). After treatment, the concentrations of IgA, IgM and IgG in the observation group were significantly higher than those before treatment (P<0.05), but only the concentrations of IgA and IgM in the control group were significantly higher than those in the observation group after treatment (P<0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group. Conclusion: Granulocyte colony-stimulating factor combined with erythropoietin can effectively correct anemia, improve nutritional status and improve immune function in patients with chronic myelogenous leukemia.

Effects of the FOXO3a rs 4946936 Gene Polymorphism on the FOXO3a Transcription Factor in Chronic Granulocytic Leukemia Patients

Introduction : FOXO3a has an important role in the maintenance of leukemic stem cells. BCR-ABL inhibition therapy by TKI dasatinib aims to reduce the phosphorylation of the transcription factor FOXO3a, promote localization of FOXO3a in the nucleus and restore transcriptional activity. However, some studies showed that the TKI dasatinib, in addition to increase the relocation of Foxo3a to the intranuclear, also increase the expression of CDKN1c/p57 and Bcl6 genes that became the down target for Foxo3a intra nucleus ATM. Therefore, current therapy is mostly directed at personalized therapy (personalized medicine). The aim of this study was to investigate the effect of the FOXO3a rs4946936 gene polymorphism on the Foxo3a transcription factor in chronic granulocytic leukemia patients treated with Imatinib mesylate. Method : This is a cross-sectional study in patients with chronic granulocytic leukemia (CGL) with positive Bcr-ABL. The aim was to prove the effect of the FOXO3a gene polymorphism rs4946936 on the Foxo3a transcription factor. The data analysis test used was a correlation test and a regression test. Result : There were three polymorphisms of the FOXO3a gene, namely CC polymorphism, TC polymorphism, and TT polymorphism with a p-value of 0.026 and an r of 0.287, so it can be concluded that there was a significant correlation between the FOXO3a gene polymorphism and the Foxo3an transcription factor with a sufficient correlation value. In the regression test between the FOXO3a gene polymorphisms and the transcription factor FOXO3a, the p value was 0.029 and the B value was -0.294. This means that it has a negative and significant effect on the Foxo3a transcription factor variable. Conclusion : There was a significant correlation between the gene polymorphism FOXO3a rs4946936 and the transcription factor FOX3a. The FOXO3a gene polymorphism of the TT genotype had a negative effect on the FOXO3a transcription factor. The TT gene in the FOXO3a gene polymorphism was the most effective in reducing the FOXO3a transcription factor.

Spontaneous splenic rupture in a patient with chronic granulocytic leukemia

Spontaneous splenic rupture is a rare phenomenon that is not associated with trauma. The most common causes of splenic rupture are hematological diseases (30.3%), inflammatory diseases (20%), infectious diseases (27.3%), drugs (9.2%), mechanical disorders (6.8%), and unknown causes (6.4%). Spontaneous splenic rupture secondary to hematological malignancy is rare; in this group of patients, chronic granulocytic leukemia is the main cause. The mechanism of spontaneous splenic rupture is uncertain. Three mechanisms have been suggested: the mechanical effect of leukemia and its infiltration in the spleen, especially if the capsule is invaded; splenic infarction with subsequent subcapsular hemorrhage and rupture of the splenic capsule, and coagulation abnormalities.

Daily Intravenous Infusion of Busulfan Impurity 5 for 4 Days Is Not Associated With Toxic Effects in the Rat

The alkylating agent busulfan is used in conditioning treatment of chronic myelogenous or granulocytic leukemia prior to stem cell transplantations. Its cytotoxic activity results in primary damage or destruction of hematopoietic cells. While the toxicity of busulfan is well investigated, little is known about the toxic effects of its impurities. In this study, the effect of 4-day intravenous infusion (3 h/d) of 4.8 mg/kg/d busulfan and 0.49, 4.9, and 49 mg/kg/d busulfan impurity 5 (4-((methylsulfonyl)oxy)butyl acetate) was investigated in rats. Whereas busulfan elicited myelotoxic and hepatotoxic effects, no toxic effects were observed in animals receiving the impurity at dosages up to 10 times higher than busulfan. The highest impurity dose of 49 mg/kg/d is therefore considered the no-observed-adverse-effect level of busulfan impurity 5.

Differences of Bone Marrow Features and BCR-ABL Variants in Chronic Granulocytic Leukemia Post Tyrosine Kinase Inhibitor Therapy

Chronic Granulocytic Leukemia (CGL) occurs due to chromosomal translocation (9;22) known as Philadelphia chromosome. p210 BCR-ABL1 oncogenes are classified into b2a2 and b3a2 transcripts which possibly lead to different clinical manifestations and response to therapy. This study was aimed to prove that there is a difference of bone marrow features and BCR-ABL between remissive and resistant CGL after Tyrosine Kinase Inhibitor (TKI) therapy. This research was an observational study with a cross-sectional design carried out at Ulin Hospital Banjarmasin on 32 subjects. BCR ABL was detected by using PCR and bone marrow features were assessed by using bone marrow aspiration technique. The difference of bone marrow features and BCR-ABL variants was analyzed by using T-test (p < 0.005) and Chi-Square (p < 0.005), respectively. There was a difference of BCR-ABL variants with p=0.091 and characterized by M:E ratio (p=0.124), myeloblast count (p=0.063), and eosinophil count (p=0.055). In addition, there was a difference of bone marrow cellularity (p=0.000) and basophil count (p=0.016) between remissive CGL and resistant CGL patients. There was no difference of BCR ABL variants, myeloblast count and eosinophil count between remissive CGL and resistant CGL patients. However, there was different of bone marrow cellularity and basophil count between remissive CGL and resistant CGL patients.

To the approximate size of the nuclear region occupied by nucleolar bodies during cell differentiation and maturation using the human leukemic granulocytic lineage as a convenient model

The present study was undertaken to estimate the approximate size of nuclear regions occupied by nucleolar bodies during the cell differentiation and maturation. The differentiation and maturation of human leukemic granulocytic cells in patients suffering from the chronic phase of the chronic granulocytic leukemia (CML) represented a convenient model for such study because of the large number of cells for the diameter measurements at the single cell level. Early and advanced differentiation or maturation stages of these cells are well defined and nucleolar bodies and nuclear outlines are easily seen by simple cytochemical methods for the visualization of RNA and silver stained proteins in smear preparations. During the cell differentiation and maturation, the estimated size of the nuclear region occupied by nucleolar bodies decreased in both untreated and treated patients with the anti-leukemic therapy. However, the size reduction of nucleolar bodies in differentiated and mature cells was larger than that of the nucleus. In addition, the results also indicated that the nuclear region occupied by nucleolar bodies was characteristic for each differentiation and maturation stage of the granulocytic cell lineage and was not substantially influenced by the anti-leukemic therapy of CML patients.