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1.
Braz. j. biol ; 84: e251336, 2024. graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1355879

ABSTRACT

Abstract Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 μg/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p < 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.


Resumo Bulbine natalensis Baker e Chorophytum comosum (Thunb.) Jacques são potenciais fontes medicinais para o tratamento de cânceres. A Leucemia Mieloide Crônica (LMC) é um distúrbio das células-tronco hematopoiéticas que é tratado com inibidores da tirosina quinase, mas frequentemente, causa recorrência da leucemia após a interrupção da terapia, portanto, requer um tratamento alternativo. Este estudo determinou o efeito anticancerígeno de extratos metanólicos e aquosos de folha, raiz e bulbo de B. natalensis e C. comosum na linhagem celular de leucemia mieloide humana crônica (K562) por ensaios de MTT, Hoechst bis-benzimida nuclear e anexina V. O extrato metanólico da raiz de B. natalensis e C. comosum apresentou alta citotoxidade de 8,6% e 16,7% respectivamente, na linhagem celular K562 com a concentração de 1,000 μg / ml. Perda morfológica da integridade da membrana celular causando degradação dos núcleos, citoplasma e encolhimento celular foi observada no extrato metanólico da raiz de ambas as plantas. Uma alta apoptose (p <0,0001) foi induzida nas células K562 por extratos de folhas e raízes de C. comosum em comparação com B. natalensis. Este estudo mostrou que ambas as plantas possuem efeito apoptótico contra leucemia mieloide in vitro que contribui para as propriedades anticâncer gerais de B. natalensis e C. comosum para justificar futuras aplicações terapêuticas contra câncer de sangue de LMC.


Subject(s)
Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Xanthorrhoeaceae , Apoptosis , K562 Cells
3.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(2): 191-200, Apr.-June 2021. tab, ilus
Article in English | LILACS | ID: biblio-1286684

ABSTRACT

ABSTRACT This manuscript summarizes the results of the consensus meeting composed of hematologists and cardiologists to establish recommendations for the prevention and follow-up of cardiovascular (CV) risk in patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKIs) from the point of view of clinical practice and from the perspective of hematology consultation.In the first medical appointment, the CV risk factors should be identified to perform the baseline risk stratification, based on the Brazilian Guideline of Dyslipidemia and Atherosclerosis Prevention Update (risk levels: very high, high, intermediate and low).Once stratified, the treatment of the CV risk factors should be administered. If the patient presents risk factors, such as hypertension, diabetes, renal disease, smoking and hypercholesterolemia, the evaluation and initial treatment may be done by the hematologist, being an option the request for evaluation by a specialist. If the patient has a history of previous CV disease, we recommend referral to a specialist. As the CV risk score is dynamic and the control of risk factors can reduce the patient risk, this expert consensus recommends that the re-evaluation of the CV risk after the baseline should be performed at 3 months, 6 months and 12 months. After this period, it should be done annually and, for specific patients, at the clinician's discretion.The evaluation of the baseline CV risk and the safe administration of a TKI allow the patient to benefit from the maximum treatment, avoiding unwanted effects.


Subject(s)
Humans , Protein-Tyrosine Kinases , Cardiovascular Diseases/therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Heart Disease Risk Factors , Tobacco Use Disorder/prevention & control , Monitoring , Diabetes Mellitus/prevention & control , Hypertension/prevention & control
4.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(1): 50-57, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1154292

ABSTRACT

ABSTRACT Introduction: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease that affects mainly adults between 50 and 55 years. In Brazil, information from the Sistema Único de Saúde (SUS) Outpatient Information System indicates that 12,531 patients had the Autorização de Procedimento Ambulatorial (APAC) approved for the CML treatment in 2017. Disease monitoring through molecular response evaluation is critical to the care of CML patients. The quantitative PCR test (real-time polymerase chain reaction) provides adequate evaluation parameters that allow the health professional to intervene at the right moments in order to reduce the chance of progression of the disease, providing the best outcome to the patient, including the possibility of treatment discontinuation for eligible patients. Although the test is included in the Clinical Protocol and Therapeutic Guidelines (PCDT) of CML, it is not possible to monitor the molecular response within SUS since there is no reimbursement for this test. Objective: Obtain expert recommendations on the importance, financing, and reimbursement of molecular monitoring in SUS. Methods: Six CML experts with different perspectives participated in the panel. The discussion was based in the main publications about the quantitative PCR test in CML monitoring. Results: Experts' recommendations: Molecular monitoring should be part of the integral treatment of patients with CML to reduce the chances of disease progression and costs to the health system; The government should put into practice what is provided in the PCDT of Chronic Myeloid Leukemia in Brazil: performing the monitoring of the molecular response via quantitative PCR; The government should create a code with adequate nomenclature and reimbursement value in SIGTAP, so that the test is carried out and covered by the public health network, as it is contained in the PCDT of the disease and the existing APAC does not cover the operational costs for its performance; Patients with chronic phase CML should perform a quantitative PCR every 3 months and, after reaching the MMR, should perform the examination every 6 months, as recommended by international guidelines; Patients should be monitored in reference laboratories that are standardized according to the international scale; The laboratories that are within the reference public centers could absorb all the test demand in Brazil, and other centers could be qualified through an ABHH accreditation; Adequate molecular monitoring may allow some patients to stop taking drugs and selffinancing the molecular test for all SUS patients Conclusion: A solution for the molecular test (BCR-ABL1) funding is urgent to ensure the monitoring of CML patients in SUS. The savings that might be generated with patients that stop taking the medication when adequately monitored may finance the test.


Subject(s)
Humans , Middle Aged , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Real-Time Polymerase Chain Reaction , Reimbursement Mechanisms , Unified Health System , Brazil , Genes, abl
5.
Rev. bras. anal. clin ; 53(1): 90-96, 20210330. tab, ilus
Article in Portuguese | LILACS | ID: biblio-1291778

ABSTRACT

Descrição: Relato de caso de um paciente com um transcrito raro (e1a2) na Leucemia Mieloide Crônica (LMC) e outro com uma translocação rara na Síndrome Mielodisplásica (SMD). Discussão: O transcrito e1a2 possui frequência de 1% entre os casos de LMC, já a translocação t(11,17)(q23;q21) não foi evidenciada em paciente com SMD do tipo Anemia Refratária com Excesso de Blastos (AREB) do tipo 2. Conclusão: Ambos os casos apresentados possuem associação incomum entre fenótipo e genótipo. A correlação da clínica com os achados laboratoriais é importante para a determinação fidedigna do diagnóstico e prognóstico destes pacientes.


Description: Case report of a patient with a rare transcript (e1a2) in Chronic Myeloid Leukemia (CML) and another with a rare translocation in Myelodysplastic Syndrome (SMD). Discussion: The transcript e1a2 has a frequency of 1% in CML cases, whereas t (11,17) (q23; q21) translocation was not observed in a patient with type of Refractory Anemia with Excess Blasts (AREB) type 2. Conclusion: Both cases reported have unusual association between phenotype and genotype. The correlation of the clinic with the laboratory findings is important for the reliable determination of the diagnosis and prognosis of these patients.


Subject(s)
Humans , Female , Middle Aged , Phenotype , Translocation, Genetic , Anemia, Refractory , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia , Hematologic Neoplasms , Genotype
6.
Autops. Case Rep ; 11: e2021339, 2021. tab, graf
Article in English | LILACS | ID: biblio-1345358

ABSTRACT

Myeloid sarcoma (MS) is a rare extramedullary neoplasm of myeloid cells, which can arise before, concurrently with, or following hematolymphoid malignancies. We report 04 such cases of MS, diagnosed in this institute over a period of 6 years, during various phases of their respective myeloid neoplasms/leukemias. These cases include MS occurring as a relapse of AML (Case 1), MS occurring as an initial presentation of CML (Case 2), MS occurring during ongoing chemotherapy in APML (Case 3), and MS presenting as a progression of MDS to AML (Case 4). In the absence of relevant clinical history and unemployment of appropriate immunohistochemical (IHC) studies, these cases have a high risk of being frequently misdiagnosed either as Non-Hodgkin's Lymphoma (NHL) or small round cell tumors or undifferentiated carcinomas, which may further delay their management, making an already bad prognosis worse. This case series has been designed to throw light on the varied presentation of MS and the lineage differentiation of its neoplastic cells through the application of relevant IHC markers along with their clinical correlation.


Subject(s)
Humans , Male , Female , Child, Preschool , Adolescent , Middle Aged , Aged , Sarcoma, Myeloid/pathology , Myelodysplastic Syndromes/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myeloid, Acute/pathology , Leukemia, Promyelocytic, Acute/pathology , Diagnostic Errors/prevention & control
7.
Braz. j. med. biol. res ; 54(8): e10685, 2021. graf
Article in English | LILACS | ID: biblio-1249326

ABSTRACT

Tanshinone I (Tan I) is one of the main bioactive ingredients derived from Salvia miltiorrhiza Bunge, which has exhibited antitumor activities toward various human cancer cells. However, its effects and underlying mechanisms on human chronic myeloid leukemia (CML) cells still require further investigation. This study determined the effects and mechanisms of anti-proliferative and apoptosis induction activity induced by Tan I against K562 cells. The cytotoxic effect of Tan I at varying concentrations on K562 cells was evaluated via MTT assay. Cell apoptosis was further investigated through DAPI staining and flow cytometry analysis. The expression levels of apoptosis-related proteins and activities of JNK/ATF2 and ERK signaling pathways were analyzed by western blot. Quantitative PCR was performed to further determine mRNA expression levels of JNK1/2 and ERK1/2 after Tan I treatment. The results indicated that Tan I significantly inhibited K562 cell growth and induced apoptosis in a concentration- and time-dependent manner. It induced significant cellular morphological changes and increased apoptosis rates in CML cells. Tan I promoted the cleavages of caspase-related proteins, as well as increased the expression levels of PUMA. Furthermore, Tan I significantly activated JNK and inhibited ATF-2 and ERK signaling pathways. The mRNA expression levels of JNK1/2 and ERK1/2 were up-regulated by Tan I, further confirming its regulatory effects on JNK/ERK signaling pathways. Overall, our results indicated that Tan I suppressed cell viability via JNK- and ERK-mediated apoptotic pathways in K562 cells, suggesting that it might be a promising candidate as a novel anti-leukemia drug.


Subject(s)
Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Abietanes/pharmacology , Apoptosis , Cell Line, Tumor
8.
Journal of Experimental Hematology ; (6): 1768-1774, 2021.
Article in Chinese | WPRIM | ID: wpr-922332

ABSTRACT

OBJECTIVE@#To investigate the effect of silencing DNA methyltransferase 1(DNMT1) to the methylation of the promoter of the tumor suppressor gene wnt-1 (WIF-1) in human chronic myeloid leukemia (CML) cells.@*METHODS@#DNMT1 siRNAi plasmid was constructed and DNMT1 siRNAi was transfected into CML K562 cells. RT-PCR and Western blot were used to detect the expression of DNMT1 gene and related protein, and methylation PCR was used to detect WIF-1 gene promoter methylation level. The trypan blue exclusion and MTT assay were used to detect the cell proliferation, flow cytometry were used to detect the cell apoptosis rate, colony formation assay was used to detect cell colony formation ability. Expression of Wnt/β- catenin and its downstream signaling pathway proteins were detected by Western blot after DNMT1 gene was silenced.@*RESULTS@#The expression level of DNMT1 mRNA and its related protein in the experimental group were significantly lower than those in the control group and negative control group (P<0.05). After 72 hours of successful transfection, the WIF-1 gene in the control group and negative control group were completely methylated, while in the experimental group, the methylation level significantly decreased. The results of MSP showed that the PCR product amplified by the unmethylated WIF-1 primer in the experimental group increased significantly,while by the methylated WIF-1 primer decreased significantly. After 48 h of transfection, the OD value, viable cell number and colony formation of the cells in experimental group were significantly lower than those in the negative control group and the control group (P<0.05). The apoptosis rate of the cells in experimental group was significantly higher than those in the negative control group and control group (P<0.05). The expression levels of β- actin, myc, cyclin D1 and TCF-1 in K562 cells in the experimental group were significantly lower than those in the negative control group and control group (P<0.05).@*CONCLUSION@#Silencing DNMT1 gene can inhibit the proliferation and promote the apoptosis of K562 cells. The mechanism may be related to reverse the hypermethylation level of the WIF-1 gene promoter, thereby inhibit the activity of the Wnt/β- catenin signaling pathway.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , DNA Methylation , Humans , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Repressor Proteins/metabolism
9.
Journal of Experimental Hematology ; (6): 1752-1756, 2021.
Article in Chinese | WPRIM | ID: wpr-922329

ABSTRACT

OBJECTIVE@#To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients.@*METHODS@#The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR.@*RESULTS@#There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months.@*CONCLUSION@#For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.


Subject(s)
Adult , Dasatinib , Female , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Middle Aged , Protein Kinase Inhibitors , Young Adult
10.
Journal of Experimental Hematology ; (6): 1746-1751, 2021.
Article in Chinese | WPRIM | ID: wpr-922328

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics of the patients with chronic myeloid leukemia (CML) discontinued tyrosine kinase inhibitors (TKI) therapy and the outcome of the patients.@*METHODS@#35 cases of CML patients experienced initiative discontinuation of TKI therapy in our hospital from June 1st 2015 to December 31th 2019 were retrospectively analyzed. The TFR of the patients and the factors affecting it were analyzed.@*RESULTS@#The median duration of TKI administration was 72 (range 35-173) months in the 35 patients. Among these patients, 8 had experienced TKI dose reduction or suspension. All the enrolled patients have achieved at least MMR. The median time for these patients achieving MMR was 15 (range 3-75) months after administration of TKI, and for MMR maintenance before TKI suspension was 55 (range 13-164) months. After TKI withdrawal the median follow up time was 20.3 (range 3-57.9) months, 22 out of 35 patients kept TFR, among them, 2 (5.71%) patients restarted TKI after 12 month suspension, and maintained MMR during suspension. 13 (37.1%)patients lost MMR, among them, 9 patients restarted TKI treatment, and 5 of them achieved MR4.0 after the median duration of 3(2-5) month. No patients were found to have disease progression. The estimated TFR rate was 57.8% and 51.8% at 12 and 24 months after discontinuation, respectively. Other clinical characteristic related to relapse were also analyzed, including the cumulative TKI administration duration, cumulative MMR duration, time to achieve MMR, median age at diagnosis, risk stratification by Sokal score, TKI dose reduction and discontinuation history, and second-generation TKI administration before stopping TKI, however, no statistical difference was found.@*CONCLUSION@#TKI discontinuation is practical for CML patients in our center.


Subject(s)
Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors , Recurrence , Retrospective Studies , Treatment Outcome
11.
Journal of Experimental Hematology ; (6): 1714-1718, 2021.
Article in Chinese | WPRIM | ID: wpr-922323

ABSTRACT

OBJECTIVE@#To investigate the regulation of chronic myelogenous leukemia (CML) imatinib resistant genes, in order to improve the therapeutic effect of CML imatinib resistant patients.@*METHODS@#The human CML cell line K562 and imatinib-resistant K562 cells (K562/G01) were collected, and transcriptome of the cells were achieved by RNA-seq. The sequencing data were analyzed by using standard procedures.@*RESULTS@#Compared with K562 cells, 464 genes were significantly changed in K562/G01 cells, including 163 up-regulated and 301 down-regulated genes. The GO function annotation analysis and KEGG pathway analysis results showed that the differentially expressed genes were mainly involved in biological processes such as oxidative phosphorylation, localization to protein organelle, ribonucleoprotein complex biogenesis and so on. Gene Set Enrichment Analysis (GSEA) plots showed that 5 gene-sets were up-regulated in K562/G01 significantly, including the pathway of TGF-beta, mTOR and CML.@*CONCLUSION@#CML imatinib resistance is associated with oxidative phosphorylation, during which the pathway of TGF-beta and mTOR are significantly up-regulated.


Subject(s)
Drug Resistance, Neoplasm , Gene Expression Profiling , Humans , Imatinib Mesylate/pharmacology , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
12.
Journal of Experimental Hematology ; (6): 1242-1246, 2021.
Article in Chinese | WPRIM | ID: wpr-888545

ABSTRACT

OBJECTIVE@#To explore the expression level of ETV6-ABL fusion gene in different cell populations in patients with myeloproliferative neoplasm (MPN) and therapeutic effect of tyrosine kinase inhibitor (TKI).@*METHODS@#A 42-year-old man who presented with fever, marked leukocytosis and chronic myelogenous leukemia (CML) like MPN was reported. ETV6-ABL fusion gene was detected by real-time PCR and confirmed by direct sequencing. ETV6-ABL mRNA expression in each cell population sorted from peripheral blood by flow cytometry was detected by real-time PCR.@*RESULTS@#ETV6-ABL fusion gene was found out in bone marrow cells and confirmed as type A by direct sequencing. ETV6-ABL fusion gene transcript level in polymorphonuclear cells was nearly 3.6-fold relative to that in total cells, which was significantly higher than that in T cell, B cell and monocyte subsets. The complete blood count (CBC) returned to normal level after treatment with imatinib (400 mg) daily for three months. After TKI treatment for 6 months, the ratio of ETV6-ABL/ABL decreased from 174.1% to 1.9%.@*CONCLUSION@#ETV6-ABL fusion gene positive MPN may have a CML clinical presentation and is sensitive to TKI. ETV6-ABL fusion gene is specifically expressed in polymorphonuclear cells.


Subject(s)
Adult , Fusion Proteins, bcr-abl/genetics , Genes, abl , Hematopoietic Stem Cell Transplantation , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Myeloproliferative Disorders/genetics
13.
Article in English | WPRIM | ID: wpr-880662

ABSTRACT

Chronic myeloid leukemia with a significant increase of monocytes is rare and difficult to identify from chronic myelo-monocytic leukemia in clinic. A 31-year-old male patient with systemic pain was initially diagnosed as chronic myelo-monocytic leukemia, who was finally diagnosed as chronic myeloid leukemia by fusion gene and chromosome examination. In addition to the typical Ph chromosome, a rare chromosome translocation t(2; 7)(p13; p22) was observed. The detection of monocyte subsets by multi-parameter flow cytometry is a diagnostic marker to distinguish the above 2 diseases. The relationship between fusion genes and mononucleosis is not clear. Tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation can be used in the treatment for this disease.


Subject(s)
Adult , Humans , Karyotype , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Monocytes , Translocation, Genetic
14.
Article in Chinese | WPRIM | ID: wpr-880097

ABSTRACT

OBJECTIVE@#To evaluate the clinical efficacy and safety of domestic imatinib (made in China) in patients with newly diagnosed chronic myeloid leukemia chronic phase(CML-CP).@*METHODS@#Fifty-seven newly diagnosed CML-CP patients who did not receive any other anti-CML treatment were treated by domestic imatinib 400 mg once a day. The hematological, cytogenetic and molecular reactions and safety were observed and evaluated after 3, 6 and 12 months of treatment.@*RESULTS@#Fifty-six patients were treated for ≥3 and 6 months, among which 50 patients were treated for ≥12 months. After 3 months of treatment, 49 patients underwent hematological examination, 47 patients (95.9%) achieved complete hematological response (CHR), 49 patients underwent cytogenetic examination, 39 patients (79.6%) achieved major cytogenetic response (MCyR), and 12 patients (24.5%) achieved complete cytogenetic response (CCyR). 49 patients underwent the level of BCR-ABL test, including 41 patients (83.7%) with BCR-ABL@*CONCLUSION@#In the real world, Domestics imatinib mesylate is effective and safe in the treatment of newly diagnosed CML-CP patients, but long-term follow-up data are still necessary to verify its long-term efficacy.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , China , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines , Pyrimidines/therapeutic use , Treatment Outcome
15.
Article in Chinese | WPRIM | ID: wpr-880087

ABSTRACT

OBJECTIVE@#To investigate the effect of etoposide (ETO) on elimination of chronic myeloid leukemia (CML) stem cells by imatinib mesylate(IM) in vivo.@*METHODS@#SCL-tTA/BCR-ABL mice were used as CML animal model. Flow cytometry was used to assess the effect of ETO alone or in combination with IM on the number of leukemia stem cell (LSC) in bone marrow and spleen, and peripheral blood neutrophils in CML mice and normal control FVB mice.@*RESULTS@#The results showed that in CML mice, the number and proportion of LSC in bone marrow and the proportion of neutrophils in peripheral blood decreased significantly after ETO and IM combined treatment, and the degree of decrease was more significant than that of both alone. While in wild type FVB mice, the combination of ETO and IM showed no significant effect on the number and proportion of LSK cells in bone marrow and the proportion of neutrophils in spleen.@*CONCLUSION@#ETO can selectively enhance elimination of CML LSC by IM in vivo.


Subject(s)
Animals , Drug Resistance, Neoplasm , Etoposide , Fusion Proteins, bcr-abl , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Mice , Stem Cells
16.
Article in Chinese | WPRIM | ID: wpr-880085

ABSTRACT

OBJECTIVE@#The present study was to evaluate the anti-tumor effects of acidic RNA protein complex (FA-2-b-β) extracted from the wild edible Qinba mushroom in inducing of apoptosis and immunoregulation of tumor cell.@*METHODS@#Cell proliferation inducing rate of FA-2-b-β to K562 cell was measured using CCK-8. Apoptosis rate was detected by using flow cytometry. Chronic myeloid leukemia model was developed by tail vein injection/subcutaneous inoculation of K562 cells in NCG mice. The tumor burden of mice was observed. The general condition of the mice was monitored twice daily. The peripherivcal full blood counts of mice was tested daily. RT-qPCR and Western blot was FA-2-b-β performed to determine involvement of apoptotic-related gene and protenin, Immunofluorescence and immunohistochemistry was used to detected the expression of CD3, CD4 and CD8.@*RESULTS@#The proliferation and apoptosis of K562 cell could be inhibitied and induced by FA-2-b-β, there was 100% successful in the tumor formation in vivo, after treated by drug for 21 days there were significantly increased peripheral leucocytes, but decreased hemoglobin of mice treated by FA-2-b-β as compared with those in control group. The CD3, CD4 and CD8 showed positive in mice, and the propotation was imbalance, but it showed reserved after treated by FA-2-b-β.@*CONCLUSION@#FA-2-b-β is strong anti-leukemia effect in vitro and in vivo, suggesting the traditional Chinese medicine maybe contribute to the anti-cancer and immunoregulation research.


Subject(s)
Agaricales , Animals , Apoptosis , Cell Proliferation , Humans , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Mice
18.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(3): 195-199, July-Sept. 2020.
Article in English | LILACS | ID: biblio-1134039

ABSTRACT

ABSTRACT The novel coronavirus has swept across the world in 2020 and ushered a new era. In the current scenario, it is not clear how patients with myeloproliferative neoplasms (including chronic myelogenous leukemia) should be managed, considering the risk of therapy, the need for social distancing and the risk of untimely therapy discontinuation of delay. This guideline aims to give providers a sense of direction in order to better take care of patients and prioritize care.


Subject(s)
Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , SARS-CoV-2 , COVID-19 , Myeloproliferative Disorders/therapy , Bone Marrow Transplantation
20.
J. venom. anim. toxins incl. trop. dis ; 26: e20200123, 2020. graf
Article in English | LILACS, VETINDEX | ID: biblio-1143219

ABSTRACT

Resistance to apoptosis in chronic myeloid leukemia (CML) is associated with constitutive tyrosine kinase activity of the Bcr-Abl oncoprotein. The deregulated expression of apoptosis-related genes and alteration in epigenetic machinery may also contribute to apoptosis resistance in CML. Tyrosine kinase inhibitors target the Bcr-Abl oncoprotein and are used in CML treatment. The resistance of CML patients to tyrosine kinase inhibitors has guided the search for new compounds that may induce apoptosis in Bcr-Abl+ leukemic cells and improve the disease treatment. Methods: In the present study, we investigated whether the L-amino acid oxidase isolated from Bothrops moojeni snake venom (BmooLAAO-I) (i) was cytotoxic to Bcr-Abl+ cell lines (HL-60.Bcr-Abl, K562-S, and K562-R), HL-60 (acute promyelocytic leukemia) cells, the non-tumor cell line HEK-293, and peripheral blood mononuclear cells (PBMC); and (ii) affected epigenetic mechanisms, including DNA methylation and microRNAs expression in vitro. Results: BmooLAAO-I induced ROS production, apoptosis, and differential DNA methylation pattern of regulatory apoptosis genes. The toxin upregulated expression of the pro-apoptotic genes BID and FADD and downregulated DFFA expression in leukemic cell lines, as well as increased miR-16 expression - whose major predicted target is the anti-apoptotic gene BCL2 - in Bcr-Abl+ cells. Conclusion: BmooLAAO-I exerts selective antitumor action mediated by H2O2 release and induces apoptosis, and alterations in epigenetic mechanisms. These results support future investigations on the effect of BmooLAAO-I on in vivo models to determine its potential in CML therapy.(AU)


Subject(s)
Animals , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Apoptosis , Bothrops , L-Amino Acid Oxidase , In Vitro Techniques
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