Depleting long noncoding RNA HOTAIR attenuates chronic myelocytic leukemia progression by binding to DNA methyltransferase 1 and inhibiting PTEN gene promoter methylation

Long noncoding RNAs (lncRNAs) are known to play a key role in chronic myelocytic leukemia (CML) development, and we aimed to identify the involvement of the lncRNA HOX antisense intergenic RNA (HOTAIR) in CML via binding to DNA methyltransferase 1 (DNMT1) to accelerate methylation of the phosphatase and tensin homolog (PTEN) gene promoter. Bone marrow samples from CML patients and normal bone marrow samples from healthy controls were collected. HOTAIR, DNMT1, DNMT3A, DNMT3B, and PTEN expression was detected. The biological characteristics of CML cells were detected. The relationship among HOTAIR, DNMT1, and PTEN was verified. Tumor volume and weight in mice injected with CML cells were tested. We found that HOTAIR and DNMT1 expression was increased and PTEN expression was decreased in CML. We also investigated whether downregulated HOTAIR or DNMT1 reduced proliferation, colony formation, invasion, and migration and increased the apoptosis rate of CML cells. Moreover, we tested whether low expression of HOTAIR or DNMT1 reduced the volume and weight of tumors in mice with CML. Collectively, the results of this studied showed that depleted HOTAIR demonstrated reduced binding to DNMT1 to suppress CML progression, which may be related to methylation of the PTEN promoter.

Analisis dan Strategi Pengendalian Model Matematika Interaksi Sel Kanker Leukemia Mielositik Kronis dan Sel Imunitas

Leukemia is a disease in the classification of cancer in the blood that is characterized by abnormal growth of blood cells in the bone marrow or lymphoid tissue, and generally occurs in leukocytes or white blood cells. White blood cells that look for types of pathogenic diseases that harm the human body and then damage it are the task of the immune system. This thesis analyzes the mathematical model of chronic myelocytic leukemia cancer cell interactions and immune cells to determine the rate of increase in the population of chronic myelocytic leukemia cancer cells to the effect of immune cells. Based on the analysis of the model obtained two equilibrium points namely the equilibrium point of the extinction of chronic myelocytic leukemia cancer cells (E0) and the equilibrium point of the coexistence of chronic myelocytic leukemia cancer cells (E1). The equilibrium point of extinction will be asymptotically stable, whereas the equilibrium point of coexistence tends to be asymptotically stable using phase fields with the help of MATLAB software. Numerical simulation results show that there is an increase in the number of chronic myelocytic leukemia cancer cell populations and a decrease in the number of vulnerable blood cell populations. When immune cells increase in population, chronic myelocytic leukemia in cancer cells decreases in population but is not significant.

Liver tumor concurrent with chronic myelocytic leukemia and extreme thrombocytosis: A rare case report

Background Chronic myelocytic leukemia (CML) may occasionally occur after organ transplantation or long-term chemotherapy for solid tumors; Solid tumors secondary to long-term chemotherapy and biotherapy in CML have also been reported. However, the concurrence of solid tumor with CML and extreme thrombocytosis in an untreated patient is seldom reported. Case presentation We describe a 61-year-old woman transferred to liver surgery department for the discovery of a large mass in the liver and an elevated plasmic AFP. She was initially diagnosed with liver cancer. Blood tests indicated a marked increase of platelets(2464x10 9 /L). The chromosome examination of bone marrow biopsy indicated the existence of t(9;22) translocation, fluorescence in situ hybridisation (FISH) and PCR were both positive for the Bcr-Abl rearrangement. The diagnosis of CML was made. She received hydroxyurea and imatinib to treat CML, and platelet-lowering therapy, and then underwent a liver biopsy, which suggestted a moderately-poorly differentiated adenocarcinoma, or might be a hepatic metastatic carcinoma. However, the patient refused further pathological examination and primary site screening for the tumor. She died six and a half months after discharge. Conclusion: Here, we describe a rare case of liver cancer concurrent with CML and extreme thrombocytosis in an old patient. However, the exact relationship between the two tumors is still unclear, and more cases are desired.

COMPARISON OF INSULIN LIKE GROWTH FACTOR-1 LEVELS IN CHRONIC MYELOCYTIC LEUKEMIA PATIENTS RECEIVING IMATINIB AND NILOTINIB THERAPY WITH HEALTHY POPULATIONS

Introduction. CML is the most common form of chronic leukemia in Indonesia, whereas in Western countries it is more commonly found in the form of chronic lymphocytic leukemia (CLL). Chronic myelocytic leukemia (CML) is a chronic myeloproliferative disease with clonal abnormalities due to genetic changes in stem cell pluripotence. This disease is characterized by proliferation of granulocyte series without differentiation disorders. On the CML, the Philadelphia chromosome (Ph1 chr) is found in a reciprocal translocation 9.22 (t9; 22). Insulin-like Growth Factor-1 is a natural polypeptide in the human body that has similarities with insulin. IGF-1 plays an important role in the growth and development of tissues. As such, several studies have shown an association between IGF-1 and -2 circulation rates. IGF-1 plays an important role in terms of stimulating cell proliferation and inhibition of apoptosis. This affects the regulation of the body's physiological growth as well as pathological growth such as cancer. Until now there has been no research on IGF-1 levels in CML patients with imatinib and nilotinib treatment. Methods. This research is a cross-sectional study, by observing the status of exposure and simultaneous disease in individuals from a single population, in one period. The study was conducted in December 2019 at the Outpatient Clinic of H Adam Malik General Hospital Medan with the approval of the North Sumatera University Research Ethics Commission. Data were analyzed using SPSS where p <0.05 was considered significant. Results. This study showed that there were no differences in IGF-1 levels between CML patients who received imatinib and nilotinib therapy. The mean IGF-1 results were obtained in the imatinib group 107.43±19.70 and nilotinib 107.43±18.09. While the healthy population is 138.60±52.85. Conclusion. No significant differences were found in IGF-1 levels between CML patients receiving imatinib and nilotinib therapy with healthy populations.

Association between Hasford Scoring System and Hematologic Response in Chronic and Accelerated Phase of Chronic Myelocytic Leukemia Patient with Imatinib for Three Months

Background: Hasford score is a scoring system which was made in interferon treatment era to assess chronic myelocytic leukemia (CML) prognosis. Complete hematologic response (CHR) is the milestone of prognosis evaluation. CHR achievement will significantly increase survival. Imatinib is a revolutionized treatment that change the prognosis of CML. With the advent of Imatinib, lessened the prognostic impact of the Hasford score to predict prognosis.Materials and Methods: An observational analytic with prospective cohort study conducted in oncology outward division Dr. Soetomo hospital Surabaya, from July until October 2018. Hasford score determined in 32 patients at the beginning of the study, given imatinib and followed up regularly for 3 months to know the hematologic response. Data were analyzed using Fisher exact test which was considered significant if p<0.05.Results: Median age was 39 years old, male 37.5% and female 62.5%, the median spleen was 18 cm, median hemoglobin was 9.1 g/dL, median leukocyte was 180x109 /L, median thrombocyte was 645x109 /L, median eosinophil was 2.9%, median basophil was 4.6%, median myeloblast was 6%. Hasford score showed 3.1% in low risk, 25% in intermediate risk and 71.9% in high risk. As much as 78.1% complete hematologic response was found in patient, and 21.9% was incomplete.Conclusion: There was no association between Hasford scoring system and hematologic response in chronic and accelerated phase of chronic myelocytic leukemia patient with imatinib for three month. Hasford score had no impact in hematologic response with imatinib.Keywords: Hasford score, hematologic response, CML, imatinib