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.

A review of current knowledge of myeloproliferative disorders in the horse

Myeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

Priapism in Patients with Chronic Myeloid Leukemia systematic Review of Case Reports

Introduction: Priapism is a persistent penile erection not associated with sexual stimulation lasting for more than 4 hours. It is seen in up to 1.9% of patients with CML in some centers. Priapism adversely affects the quality of life, sexual function, of the affected patients. Long-lasting priapism is associated with a drastic effect on male fertility. The underlying pathophysiology involves disturbed autoregulation of the penile circulation through nitrous oxide (NO) and phosphodiesterase enzyme dysregulation. Method Literature searched in google scholar, PubMed, and Scopus search engines with keywords priapism, chronic myeloid leukemia, chronic granulocytic leukemia, and chronic myelogenous leukemia (English literature between 1960 to 2020) Results One hundred cases of priapism were reported in patients with CML. Most patients were below the age of 40 with mean 27.4years. The youngest was 7 weeks old and the oldest was 60 years old. Most patients had priapism as the first presentation of CM, 3 developed priapism after starting the treatment, 2 after stopping treatment, one noncompliant with treatment,1 previously diagnosed, and 1 patient post-splenectomy. The majority of patients' priapism occurred during the chronic phase of the disease and only 5/100 had priapism during the blast and accelerated phase. They had a mean WBC = 321.29 × 109/ (n=92), and mean platelet count = 569,000 (n=69). The lowest WBC count associated with priapism was 37 x10^9/L, the highest was 782 x10^9/L. Treatment modalities included medications, aspiration and irrigation of the corpora cavernosa, radiation to the penis, leukoreduction, and surgical shunts. Medications were used in (N = 50), aspiration of the corpora cavernosa in (N = 45) patients, leukapheresis in (N = 14), radiotherapy in (N= 9), and shunt in (N = 32). Surgical shunt relieved priapism in (N = 16), another 5 had shunt with partial response and needed chemotherapy to control the priapism. 19 patients responded to aspiration and irrigation, and another 2 required chemotherapy to control priapism. Radiation was helpful in resolving the priapism in 3 patients and Leukapheresis was useful in 5 patients. Medications alone were used to terminate priapism in 10 patients, however, priapism persisted for a longer duration compared to other modalities. It has been known that priapism lasting &gt; 24 hours poses a high risk of permanent erectile dysfunction (94% or more). In 76 of CML patients with priapism, the mean time from onset to the presentation was 78.28 hours (three times longer than the high-risk period). The erectile function was affected in 24/100, not affected in 15/100, and not addressed in 61/100. Conclusion: Although priapism is an uncommon complication of CML, its fast diagnosis and management is crucial to avoid permanent erectile dysfunction. Disclosures No relevant conflicts of interest to declare.

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.

Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, chronic myelocytic leukemia, and chronic granulocytic leukemia, is characterized by the expansion of myeloid progenitor cells at various stages of maturation, their premature release into the circulation, and a tendency to home to extramedullary sites. Symptoms at presentation reflect the increase in mass and turnover of the leukemic cells, although as many as 50% of patients are asymptomatic at diagnosis and come to attention through unexpected findings on routine blood tests. In treatment, the ongoing development of established and novel tyrosine kinase inhibitors (TKIs) has made for closer to normal life spans in patients diagnosed with CML. This review serves as an overview of CML, detailing its epidemiology and etiology, pathophysiology, diagnosis, treatment (including an assessment of the latest clinical trials involving TKIs), and management of patients with advanced phases. Figures show BCR-ABL signaling pathways and mechanisms of resistance to imatinib. Tables list stages of CML, differential diagnosis of CML and Philadelphia chromosome–negative myeloproliferative disorders, a summary of pivotal phase III trials of approved TKIs for the treatment of front-line or relapsed CML, response evaluation to TKIs used as first-line therapy, and a summary of important phase II trials of second- and third-generation TKIs after previous TKI failure. This review contains 2 highly rendered figures, 5 tables, and 87 references.