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1.
Lancet Oncol ; 21(10): e477-e487, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002443

RESUMO

The use of total body irradiation as part of conditioning regimens for acute leukaemia is progressively declining because of concerns of late toxic effects and the introduction of radiation-free regimens. Total marrow irradiation and total marrow and lymphoid irradiation represent more targeted forms of radiotherapy compared with total body irradiation that have the potential to decrease toxicity and escalate the dose to the bone marrow for high-risk patients. We review the technological basis and the clinical development of total marrow irradiation and total marrow and lymphoid irradiation, highlighting both the possible advantages as well as the current roadblocks for widespread implementation among transplantation units. The exact role of total marrow irradiation or total marrow and lymphoid irradiation in new conditioning regimens seems dependent on its technological implementation, aiming to make the whole procedure less time consuming, more streamlined, and easier to integrate into the clinical workflow. We also foresee a role for computer-assisted planning, as a way to improve planning and delivery and to incorporate total marrow irradiation and total marrow and lymphoid irradiation in multi-centric phase 2-3 trials.


Assuntos
Transplante de Medula Óssea , Medula Óssea/efeitos da radiação , Leucemia Mieloide Aguda/terapia , Irradiação Linfática , Condicionamento Pré-Transplante , Humanos , Irradiação Linfática/efeitos adversos , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/tendências , Resultado do Tratamento , Irradiação Corporal Total/efeitos adversos
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1433-1439, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067933

RESUMO

OBJECTIVE: To study the difference of long non coding RNA (lncRNA) expression profile in bone marrow specimens of children with acute leukemia (AL) and other hematological disease children with normal bone marrows as controls, to screen the lncRNA related with childhood hematological diseases, and to explore the expression of lncRNA AC002454.1 and its clinical significance in AL children. METHODS: The microarray gene chip technology was used to statistically analyze the lncRNA in bone marrow cells of newly diagnose AL children and control children. Ninty-seren differentially expressed lncRNAs were selected. The bone marrow specimens of ALL children (21 cases), AML children (22 cases) and control children (21 cases) were verified and compared by using qRT-PCR; then the lncRNA with maximum differential expression-lncRNA AC002454.1 was selected and used to analyze the relation of relative expression level with clinical indicators. RESULTS: The microarray gene chip detection showed that 1 884 differentially expressed lncRNA were found in ALL children, and 4 289 differentically expressed lncRNA were found in AML children. The results confirming these differentically expressed lncRNA by qRT-PCR showed that 9 lncRNA expression were significantly up-regulated in ALL children, and 12 lncRNA expression were significantly up-regulated in AML children. Among these up-regulated lncRNA, the difference of AC002454.1 expression was most significant in ALL and AML children (P<0.05, P<0.01). The detection showed that there was a significant difference, in AC002454.1 relative expression level of newly diagnosed T-ALL and B-ALL children (P<0.01), moreover, this difference also was found in ALL and AML children (P<0.05). The detection analysis showed that there was no statistical difference in AC002454.1 relative expression level among the different sex, age, WBC count at initial diagnosis, chromosome, fusion gene, and risk stratification (P>0.05 for all). CONCLUSION: The lncRNA expression profile of AL children has been gained by using the lncRNA microarray gene chip technicology. AC002454.1 the significantly high expression exist in AL children, which relates with immunotyping and prognosis of AL children in a certain degree.


Assuntos
Leucemia Mieloide Aguda , RNA Longo não Codificante , Doença Aguda , Criança , Humanos , Leucemia Mieloide Aguda/genética , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Longo não Codificante/genética
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1440-1444, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067934

RESUMO

OBJECTIVE: To explore the efficacy and adverse reactions of decitabine combined with reduction FLAG regimen on the senile patients with high-risk AML. METHODS: 12 senile patients with high-risk AML received decitabine combined with reduced FLAG regimen (decitabine 20 mg/m2, intravenous drip, qd, d 1-5; fludarabine 30 mg/m2, intravenous drip lasts 30 min, qd, d 3-6; Ara-C 1 g/m2, intravenous drip, qd, d 3-6; and G-CSF 300 µg/d, subcu- taneous injection, d 2 to neutrophils reached the lowest return to>1.0×109/L) in our study. The efficacy and adverse reactions of this regimen were analyzed. RESULTS: 9 patients achieved complete remission(CR) after one course of decitabine combined with reduced FLAG regimen, 2 patients achieved partial remission (PR) and 1 patient reached a stable disease (SD). The overall response rate was 92%. The median follow-up period was 7.4 months ranged from 3 to 12 months. The median survival time for all patients was 6.4 months. The main treatment-related toxicities were myelosuppression and infection due to neutropenia. Severe non-hematologic toxicities were not observed in these patients, and there was no treatment-related mortality. CONCLUSION: Decitabine combined with reduced FLAG regimen has a definite clinical efficacy in the treatment of senile patients with high-risk AML. This regimen, as induction remission regimen, can effectively improve the CR rate and reduce the adverse reactions. Therefore, it may be used as one of the preferred induction remission regimen to treat the senile patients with high-risk AML.


Assuntos
Decitabina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/uso terapêutico , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Resultado do Tratamento
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1445-1450, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067935

RESUMO

OBJECTIVE: To study the molecular characteristics and clinical significance of elderly patients with acute myeloid leukemia (AML). METHODS: Dideoxy sequencing was used to analyze the mutation spectrum and clinical significance of 51 hematopathy-related genes in 52 patients with newly diagnosed elderly AML. The efficacy of 39 patients receiving DCAG chemotherapy was also analyzed. RESULTS: The mutational frequency was high in elderly AML patients (98.1%, 51/52), and there were some coexistence or mutual exclusion between different mutations. Both the number of mutations and the incidence of epigenetic mutations DNMT3A, TET2 (P<0.01), as well as FLT3-ITD (P<0.05) increased with age. c-KIT mutations were most common in favorable-risk AML (P<0.01), while NPM1 and DNMT3A were common in intermediate-risk AML (P<0.05), especially in AML with normal karyotype. The complete remission rate of elderly AML patients receiving DCAG chemotherapy was 71.8% (28/39). CONCLUSION: Elderly AML patients have specific molecular characteristics, and the incidence of methylation-related gene mutations is very high, showing a certain significance for clinical diagnosis and treatment.


Assuntos
Leucemia Mieloide Aguda , Proteínas Nucleares , Idoso , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Taxa de Mutação , Proteínas Nucleares/genética , Prognóstico
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1480-1485, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067941

RESUMO

OBJECTIVE: To investigate the correlation of NK cell receptor-interacting serine/threonine kinase 1(RIPK1) activity and expression with prognosis of acute myeloid leukemia (AML) patients with FLT3-ITD mutation. METHODS: A total of 132 AML patients with FLT3-ITD mutation and 136 AML patients with FLT3-WT were selected. Clinical data and the number, length and rearrangement ratio of FLT3-ITD mutations were collected. The ratio of CD4+ T cells, regulatory T cells(Tregs), CD8+ T cells, B cells, natural killer cells(NK cells) and macrophage in peripheral blood(PB) were analyzed by flow cytometry. Correlation of NK cell ratio with FLT3-ITD mutation number, length and rearrangement ratio was analyzed by Pearson correlation analysis. Western blot and RT-qPCR were used to detect RIPK1 protein and mRNA levels in NK cells, respectively. Plasma RIPK activity was detected by ELISA, and Pearson corre-lation analysis was performed for the correlation of RIPK with FLT3-ITD mutation number, length and rearrangement ratio. Kaplan-Meier curve was used to analyze the survival rate of AML patients with FLT3-ITD mutation. RESULTS: Compared with AML patients with FLT3-WT, the white blood cell count in patients with FLT3-ITD mutation significantly increased, PB and BM blasts significantly decreased. There was no significant change in PB CD3+ T cells, Tregs, CD8+ T cells, B cells, M1 and M2 type macrophage of AML patients with FLT3-WT and FLT3-ITD mutation;Compared with AML patients with FLT3-WT, CD4+ T cells significantly decreased, NK cells significantly increased in AML patients wtih FLT3-ITD mutation. NK cells ratio in AML patients with FLT3-ITD mutation significantly positively correlated with the number of FLT3-ITD mutations and rearrangement bases. Plasma RIPK1 activity, RIPK1 protein and mRNA levels in NK cells of AML patients with FLT3-ITD were significantly lower than those of AML patients with FLT3-WT, and negatively correlated with the number of FLT3-ITD mutations, the length of rearranged bases (≥52 bp) and the ratio of rearranged bases. The survival rate of AML patients with FLT3-ITD mutation in low RIPK1 activity after Rydapt treatment was significantly higher than that in high RIPK1 activity. CONCLUSION: The prognosis of AML patients with FLT3-ITD mutation closely relates with plasma RIPK1 activity and RIPK1 expression in NK cells.


Assuntos
Linfócitos T CD8-Positivos , Leucemia Mieloide Aguda , Humanos , Células Matadoras Naturais , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico , Proteína Serina-Treonina Quinases de Interação com Receptores , Tirosina Quinase 3 Semelhante a fms/genética
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1491-1495, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067943

RESUMO

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment methods of patients with myeloid sarcoma(MS). Methods: The clinical data, laboratory examination, clinical pathology and treatment methods of 15 patients with MS treated in the First Affiliated Hospital of Wannan Medical College from June 2012 to January 2020 were retrospectively analyzed. RESULTS: Among the 15 cases of MS, including eight males and seven females, the middle age of patients were 53(19 to 72). Among the 15 patients with MS, 4 showed solitary MS, while 11 showed secondary MS. Immunohistochemical results showed that MPO+(12/15)、CD68+(3/6)、Lys+(3/3)、CD34+(6/14)、TdT+(0/9)、CD43+(13/13)、CD117+(6/10)、CD15+(7/10)、CD3+(1/15)、CD20+(0/15). 6 of 13 patients were survival till follow-up date.The median overall survival (OS) time was 16 months (1-88 months).Conclusion: Myeloid sarcoma is rare and often secondary from acute myeloid leukemia(AML) and chronic myeogenous leukemia(CML). Isolated MS can easily be misdiagnosed as lymphoma. Treatment response should be evaluated in combination with bone marrow examination, PET/CT and other imagines.Systematic chemotherapy and hematopoietic stem cell transplantation are the main method to treat MS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sarcoma Mieloide , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1496-1503, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067944

RESUMO

OBJECTIVE: To explore the correlation of SOCS1 gene methylation with the activity of JAK2/STAT signaling pathway, genesis and progress of acute myeloid leukemia. METHODS: Several techniques, such as cell culture, qPCR, MS-PCR, Western bolt, CCK-8 assay, flow cytometry and gene transfection were used to analyze the relation of expression and methylation statues of SOCS1 gene with the genesis and progression of AML in 120 AML patients and leukemia cell lines U937 and THP-1, at the same time to analyze the changes of downstream protein expression in JAK2/STAT signaling pathway and their effect on the growth and apoptosis of leukemia cell lines. RESULTS: The positive rate of WT1/ABL in SOCS1 methylated group was significantly higher than that in SOCS1 non-methylated group, and the complete remission rate of one course treatment in SOCS1-methylated group was significantly lower than that in SOCS1 non-methylated group. The expression level of SOCS1 gene in low methylation rate group was higher, and the expression of down-stream proteins p-JAK2, p-STAT3 and p-STAT5 in JAK2/STAT signaling pathway decreased, while the expression of t-JAK2,t-STAT3 and t-STAT5 was not changed statistically significantly. The growth rate of leukemia cells graduated decreased, and the apoptosis rate of leukemia cells graduated increased along with the enhancement of methylation drug concentration. CONCLUSION: The methylation of SOCS1 gene results in the gene silencing, thereby declines its inhibition on the down-stream proteins in JAK2/STAT signaling pathway, and finally promotes the growth and proliferation of AML cells.


Assuntos
Leucemia Mieloide Aguda , Apoptose , Humanos , Janus Quinase 2 , Leucemia Mieloide Aguda/genética , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1510-1515, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067946

RESUMO

OBJECTIVE: To investigate the clinical prognostic factors of initially-treated AML children with t(8;21)/RUNX1-RUNX1T1+. METHODS: Clinical data of 41 initially-treated AML children with t(8;21)/RUNX1-RUNX1T1+ in our hospital in period from January 2009 to January 2017 were retrospectively analyzed. The baseline clinical characteristics, cumulative recurrence, event-free survival (EFS) and overall survival (OS) were recorded, and the influencing factors of prognosis were evaluated by χ2 test and Cox regression model. RESULTS: The complete remission (CR) rates in the first course and the second course of induction chemotherapy were respectively 82.93% (34/41) and 97.56% (40/41). The median EFS time and OS time were 30 months and 31 months respectively. The EFS rate and OS rate of children with CR after the first treatment course were significantly higher than those of children without CR (P<0.05). The EFS rate of male children was significantly higher than that of female children (P<0.05). The OS rate of children < 10 years old was significantly higher than that of children≥10 years old (P<0.05). The expression level of RUNX1-RUNX1T1 gene after the second induction remission was the influencing factor of cumulative recurrence rate, EFS rate and OS rate in children (P<0.05). Multivariate analysis by Cox regression model showed that the decreased levels of RUNX1-RUNX1T1 gene expression < 3 log after the second induction remission was the independent risk factor for EFS rate and OS rate in children (P<0.05). The cumulative recurrence rate of children with RUNX1-RUNX1T1 gene expression increase for>1 log after decreased 3 log was significantly higher than that of children with≤1 log (P<0.05). CONCLUSION: Iuithally-treated AML children with t(8;21)/RUNX1-RUNX1T1+ show the fine clinical prognosis after standard chemotherapy. The expression level of RUNX1-RUNX1T1 gene should be closely relates with the recurrence and long-term survival of AML children.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Criança , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Recidiva Local de Neoplasia , Prognóstico , Proteína 1 Parceira de Translocação de RUNX1 , Estudos Retrospectivos
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1516-1522, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067947

RESUMO

OBJECTIVE: To investigate the short-term and long-term curative efficacy of low-intensity traditional chemotherapy regimen for elderly patients with acute myeloid leukemia (AML, non-M3) and related adverse reactions, in order to explore whether low-intensity traditional chemotherapy regimen still has application value in the treatment of elderly AML patients today. METHODS: The clinical characteristics, treatment response and prognosis of 67 elderly patients with AML (non-M3) admitted to our hospital from June 2008 to December 2018 were retrospectively analyzed. All patients received low-intensity conventional chemotherapy (i.e. lower standard dose, and without new drugs listed in China since the 21st century), including DA, HA, CAG, etc. The CR rate, median survival time and 5-year cumulative survival rate of patients were evaluated, and the related indexes were compared with the data reported in domestic and foreign literatures at the same time. RESULTS: The CR rate was 55.2% (37/67), the median survival time was 13.7 months, and the 5-year cumulative survival rate was (24.4±6.3)% in patients received low-intensity tradional chemotherapeutic regimens. The CR rates of high-risk group and non-high-risk group were 38.7% (12/31) and 69.4% (25/36), respectively; the median survival time of high-risk group and non-high-risk group was 8.9 months and 25.2 months respectively; the 5-year cumulative survival rate of high-risk group was (10.2±6.6)% and that of non-high-risk group was (36.0± 9.4)%. Compared with the data reported in the literature at the same time, the data obtained from the low-intensity traditional chemotherapy regimen for the elderly AML did not have an obvious disadvantage, morever had relatively short bone marrow suppression time, low induction early mortality rate and low incidence of severe infection. CONCLUSION: At present, the low-intensity traditional chemotherapy regimen still has good curative effect and survival advantages for elderly AML patients, especially for non-high-risk patients. The adverse reactions are controllable, and the physical and economic conditions of the vast majority of patients can bear the treatment regimen.


Assuntos
Citarabina , Leucemia Mieloide Aguda , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , China , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1539-1544, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067951

RESUMO

OBJECTIVE: To detect the expression level of LncRNA XLOC_109948 in bone marrow and serum of patients with acute myeloid Leukemia (AML), to verify the consistency between the expression in bone marrow and serum and to explore the role of LncRNA XLOC_109948 expression in the occurrence a development of AML. METHODS: Bone marrow and peripheral blood samples were collected from 62 patients with AML, including 36 patients with AML (AML group), 26 AML patients with complete remission (AML-CR group), and peripheral blood from 20 healthy persons (control group) were also collected. The expression level of LncRNA XLOC_109948 was detected by real-time quantitative fluorescence PCR (qRT-PCR), and the relationship between its expression and clinical characteristics was analyzed. RESULTS: The expression of LncRNA XLOC_109948 in bone marrow and serum of AML patients was higher than that of AML patients with complete remission and healthy people (P<0.001). And there was no statistically significant difference between the AML-CR group and control group (P>0.05). The expression of LncRNA XLOC_109948 significantly decreased when AML patients reached to CR, and significantly increased when the disease relapsed (P<0.05). The expression of LncRNA XLOC_109948 significantly correlated with the clinicopathologic parameters of cytogenetics (P<0.05), but not significantly correlated with sex, age, WBC count, blast in bone marrow, FAB classification and other clinical characteristics (P>0.05). CONCLUSION: The expression of LncRNA XLOC_109948 in bone marrow and serum of AML patients is high, and its expression in time and sequence is consistent between bone marrow and serum, which can reflect the occurrence, development, chemotherapy efficacy and prognosis of AML patients.


Assuntos
Leucemia Mieloide Aguda , RNA Longo não Codificante , Medula Óssea , Humanos , Leucemia Mieloide Aguda/genética , Prognóstico , RNA Longo não Codificante/genética , Indução de Remissão
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1545-1550, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067952

RESUMO

OBJECTIVE: To investigate the expression and mechanism of histone acetyltransferase 2A (KAT2A) and cyclin D1 dependent kinase 4/6 (CDK4/CDK6) in children with acute leukemia(AL). METHODS: Seventy-one children with leukemia were selected from June 2017 to November 2018 and were enrolled in AL children group. 59 persons of healthy physical examination were selected and enrolled in control group. Real-time fluorescent quantification PCR chip was used to determine the expression of histone-modified genes and the expression levels of CDK4, CDK6 and CDK4/CDK6 mRNA; Western blot was used to validated KAT2A-positive expression; SPSS Pearson correlation analysis software was used to analyze the correlation between KAT2A and CDK4/CDK6 expression in children with acute leukemia. RESULTS: By comprehensive analysis of the existing chip data, the positive expression of KAT2A in the AL children group was 78.87%, which was higher than that in the control group (8.47%) (P<0.05). The expression level of CDK4 and CDK6 mRNA in the AL children group was higher than that in the control group (P<0.05); the expression level of CDK4/CDK6 mRNA in the AL children group was lower than that in the control group (P<0.05). The results of Western blot showed that the expression levels of KAT2A, CDK4 and CDK6 in AL children were higher than those in the control group, while the CDK4/CDK6 expression level in AL children group was lower than that in control group. The results of SPSS Pearson correlation analysis showed that the positive expression rate of KAT2A in AL children group positively correlated with expression level of CDK4 and CDK6 mRNA(r=0.673, r=0.559), and negatively correlated with expression level of CDK4/CDK6 mRNA(r=-0.762). CONCLUSION: The KAT2A is highly expressed in AL children, while the CDK4/CDK6 is lowly expressed in AL children, there is a significant correlation between of them, which is expected to become a new target for the treatment of acute leukemia children.


Assuntos
Histonas , Leucemia Mieloide Aguda , Criança , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Histona Acetiltransferases , Humanos , RNA Mensageiro
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1637-1642, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067966

RESUMO

OBJECTIVE: To study the expression of Shh singaling related gene, including Shh, Ptch1, Smo and Gli1 in bone marrow CD34+ cells of patients with myelodysplastic syndrome(MDS) and acute myeloid leukemia with myelodysplasia-related changes(AML-MRC), and to explore their clinical significance. METHODS: The count of CD34+ cells in bone marrow was detected by flow cytometry in 53 patients with MDS and 30 patients with AML-MRC. Magnetic beads were used to separate CD34+ cells. The expression of Shh, Ptch1,Smo and Gli1 on CD34+ cells was detected by qRT-PCR, the effect of the 4 gene expression on prognosis of patients in MDS and AML-MRC group was compared, 25 patients with iron-deficiency anemia were used as controls. RESULTS: The expression levels of Shh, Smo and Gli1 of patients in MDS and AML-MRC group were significantly higher than those in control group (P<0.05), moreover increased with disease progression(P<0.05). The expression of Ptch1 was not statistically significantly different between 3 groups(P>0.05). In comparison of prognosis, the expression of Smo and Gli1 in the patients of relatively high risk groups and AML-MRC groups were significantly increased (P<0.05). The median overall survival time of patients in MDS and AML-MRC groups was 12(7.5,16.5) and 6(3.0,9.0) months (P=0.000) respectively. The median survival time of MDS and AML-MRC patients with high expression of Smo and Gli1 was significantly shorter than that of MDS and AML-MRC patients with low expression of Smo and Gli1(P<0.05). CONCLUSION: Shh signaling pathway in the patients with MDS is activated, which is involved in the progress and prognosis of MDS.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Medula Óssea , Células da Medula Óssea , Proteínas Hedgehog , Humanos , Transdução de Sinais
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1464-1467, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067938

RESUMO

OBJECTIVE: To investigate the prognostic significance of CUEDC1 in patients with acute myeloid leukemia (non-M3). METHODS: 52 cases newly diagnosed AML (non-M3) were selected and enrolled in AML non-M3 group, at the same time, 10 cases of iron doficiency anemia were selected and enrolled in control group. The bone marrow mononuclear cells(BMMC) were isolated from bone marrow of patients, the expression level of CUEDC1 in BMMC was detected by RT-PCR, the expression level of CUEDC1 mRNA in BMMC of AML-subtype patients was compared. The AML patients were divided into low and high expression groups according to the expression level of CUEDC1 mRNA, and the complete remission rate after the first chemothrapy course was compared, and the relative expression level of CUEDC1 mRNA between the remission and the non-remission group were compared. RESULTS: CUEDC1 was expressed in BMMC of 52 newly diagnosed patients with AML (non-M3) of all subtypes, which was higher than that in control group (P<0.05), and the expression level of CUEDC1 mRNA in M5 patients was the highest (P<0.05). In CUEDC1 low expression group, induced complete remisson rate (76.2%,16/21) after the first course of treatment seemed higher than that of the high expression group(67.7%,21/31), but the difference was not statistically significant; the expression level of CUEDC1 mRNA in the remission group of patients with newly diagnosed AML(non-M3) was lower than that in the non-remission group(P<0.05). CONCLUSION: CUEDC1 is highly expressed in newly diagnosed patients with AML, among which the CUEDC1 mRNA expression level in M5 patients is the highest, the expression of CUEDC1 mRNA possibly relates to the prognosis of patients with AML.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Leucemia Mieloide Aguda , Medula Óssea , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Ferro , Prognóstico , RNA Mensageiro/genética
14.
Medicine (Baltimore) ; 99(40): e22488, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019444

RESUMO

RATIONALE: Some acute myeloid leukemia (AML) patients present with features mimicking the classical hypergranular subtype of acute promyelocytic leukemia (APL) but without the typical promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement. Herein, we report an AML patient resembling APL but with nucleoporin 98/retinoid acid receptor gamma gene (NUP98/RARG) fusion transcript and Runt-related transcription factor 1 (RUNX1) mutation. PATIENT CONCERNS: An 18-year-old male presented at the hospital with a diagnosis of AML. DIAGNOSES: The patient was diagnosed with bone marrow examination. Bone marrow smear displayed 90.5% promyelocytes. Fluorescence in situ hybridization analysis failed to detect the PML/RARα fusion transcript or RARα amplification. While real-time polymerase chain reaction showed positivity for the NUP98/RARG fusion transcript. G-banding karyotype analysis showed a normal karyotype. INTERVENTIONS: The patient showed resistance to arsenic trioxide and standard 3 + 7 chemotherapy, but eventually achieved complete remission through the Homoharringtonine, Cytarabine, and Aclarubicin chemotherapy. OUTCOMES: These measures resulted in a rapid response and disease control. LESSONS: Acute myeloid leukemia with the NUP98/RARG fusion gene and the RUNX1 mutation may be a special subtype of AML and may benefit from the alkaloid-based regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Adolescente , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Diagnóstico Diferencial , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Promielocítica Aguda/diagnóstico , Masculino , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Receptores do Ácido Retinoico/genética
15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5482-5485, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019220

RESUMO

Acute leukemia often comes with life-threatening prognosis outcome and remains a critical clinical issue today. The implementation of measurable residual disease (MRD) using flow cytometry (FC) is highly effective but the interpretation is time-consuming and suffers from physician idiosyncrasy. Recent machine learning algorithms have been proposed to automatically classify acute leukemia samples with and without MRD to address this clinical need. However, most prior works either validate only on a small data cohort or focus on one specific type of leukemia which lacks generalization. In this work, we propose a transfer learning approach in performing automatic MRD classification that takes advantage of a large scale acute myeloid leukemia (AML) database to facilitate better learning on a small cohort of acute lymphoblastic leukemia (ALL). Specifically, we develop a knowledge-reserved distilled AML pre-trained network with ALL complementary learning to enhance the ALL MRD classification. Our framework achieves 84.5% averaged AUC which shows its transferability across acute leukemia, and our further analysis reveals that younger and elder ALL patient samples benefit more from using the pre-trained AML model.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Destilação , Humanos , Leucemia Mieloide Aguda/diagnóstico , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico
16.
Tumour Biol ; 42(9): 1010428320954735, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32873193

RESUMO

Acute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. Although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve patient outcome and minimize toxicity is needed. In this study, the antitumor activity of axolotl (AXO) Ambystoma mexicanum crude extract was assessed in vitro on the human acute myeloid leukemia HL-60 cell line. The anticancer activity was evaluated in terms of ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation. Moreover, gene expression analysis was performed to evaluate the genes involved in the regulation of these processes. The AXO crude extract exhibited antiproliferative but not cytotoxic activities on HL-60 cells, with cell cycle arrest in the G0/G1 phase. Furthermore, the AXO-treated HL-60 cells showed an increase in both the percentage of nitroblue tetrazolium positive cells and the expression of CD11b, whereas the proportion of CD14-positive cells did not change, suggesting that extract is able to induce differentiation toward the granulocytic lineage. Finally, the treatment with AXO extract caused upregulation of CEBPA, CEBPB, CEBPE, SPI1, CDKN1A, and CDKN2C, and downregulation of c-MYC. Our data clearly show the potential anticancer activity of Ambystoma mexicanum on HL-60 cells and suggest that it could help develop promising therapeutic agents for the treatment of acute myeloid leukemia.


Assuntos
Ambystoma mexicanum , Proliferação de Células/efeitos dos fármacos , Misturas Complexas/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p18/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Proteínas Proto-Oncogênicas c-myc/genética
17.
Medicine (Baltimore) ; 99(35): e21848, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871908

RESUMO

RATIONALE: Drug-induced pancreatitis (DIP) is a kind of acute pancreatitis with a relatively low incidence. There are many cases of acute pancreatitis (AP) caused by chemotherapeutic agents that have been reported. However, few reports focus on the combination of chemotherapeutic agents that induce acute pancreatitis. This article aims to retrospectively analyze a case of DIP and to explore the relationship between chemotherapeutic agents and acute pancreatitis. PATIENT CONCERNS: Here, we report a 35-year-old Chinese female patient who was diagnosed as acute myeloid leukemia with BCR/ABL expression. After induction chemotherapy of daunorubicin and cytarabine, bone marrow aspiration showed: Acute myeloid leukemia-not relieved (AML-NR). Then the regimen of homoharringtonine, cytarabine and dasatinib was started. The patient developed abdominal pain on the 14th day of chemotherapy. Laboratory tests showed elevated serum amylase (AMY) and lipase (LIPA). Computed tomography (CT) of the abdomen revealed a swollen pancreas with blurred edges and thickened left prerenal fascia. DIAGNOSIS: The patient was diagnosed as DIP by the symptoms of upper abdominal pain and the change of CT images. Other common causes of AP were excluded meanwhile. INTERVENTIONS: The chemotherapy was stopped immediately. And after fasting, fluid infusion and inhibiting the secretion of the pancreas, the symptoms were relieved. OUTCOMES: DIP relapsed when the regimen of aclacinomycin + cytarabine + G-CSF + dasatinib regimen (G-CSF (400ug/day, day 1 to 15), cytarabine (30 mg/day, day 2 to 15), aclacinomycin (20 mg/day, day 2 to 5)and dasatinib (140 mg/day, continuously)) was given, and was recovered after treatment for AP was performed. LESSONS: To choose the best treatment plan for patients, clinicians should raise awareness of DIP, and should know that chemotherapeutic agents can induce pancreatitis and the combination of chemotherapeutic agents may increase the risk of drug-induced pancreatitis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Pancreatite/induzido quimicamente , Adulto , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Feminino , Mepesuccinato de Omacetaxina/administração & dosagem , Mepesuccinato de Omacetaxina/efeitos adversos , Humanos , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada por Raios X
18.
Medicine (Baltimore) ; 99(35): e22047, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871963

RESUMO

BACKGROUND: We identified the hub genes and pathways dysregulated in acute myeloid leukemia and the potential molecular mechanisms involved. METHODS: We downloaded the GSE15061 gene expression dataset from the Gene Expression Omnibus database and used weighted gene co-expression network analysis to identify hub genes. Differential expression of the genes was evaluated using the limma package in R software. Subsequently, we built a protein-protein interaction network followed by functional enrichment analysis. Then, the prognostic significance of gene expression was explored in terms of overall survival. Finally, transcription factor-mRNA (ribonucleic acid) and microRNA-mRNA interaction analysis was also explored. RESULTS: We identified 100 differentially expressed hub genes. Functional enrichment analysis indicated that the genes were principally involved in immune system regulation, host defense, and negative regulation of apoptosis and myeloid cell differentiation. We identified 4 hub genes, the expression of which was significantly correlated with overall survival. Finally, 26 key regulators for hub genes and 38 microRNA-mRNA interactions were identified. CONCLUSION: We performed a comprehensive bioinformatics analysis of hub genes potentially involved in acute myeloid leukemia development. Further molecular biological experiments are required to confirm the roles played by these genes.


Assuntos
Leucemia Mieloide Aguda/metabolismo , Biologia Computacional , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , MicroRNAs/metabolismo , Mapas de Interação de Proteínas , Análise de Sobrevida , Fatores de Transcrição/metabolismo , Transcriptoma
19.
Medicine (Baltimore) ; 99(35): e22064, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871966

RESUMO

RATIONALE: Patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have poor prognosis. Many patients are not eligible for 2nd HSCT due to organ dysfunction or other complications that prevent them from tolerating conditioning chemotherapy. In those ineligible patients for 2nd HSCT with myeloablative conditioning regimen, reduced intensity conditioning (RIC) are often used. RIC regimens are less toxic but has a less direct anti-tumor efficacy so that RIC regimens are not suitable for the patients with high tumor burden. To overcome this dilemma, Gemtuzumab Ozogamicin (GO) has been used as a part of RIC regimens to add anti-tumor efficacy. We report here a relapsed AML patient who was treated with GO monotherapy followed by stem cell infusion. PATIENT CONCERNS: A 25-year-old male with AML experienced relapse 9 months after allo-HSCT. DIAGNOSIS: Since he had mild renal and cardiac dysfunction and his AML did not progress rapidly, we decided not to give him an intensive chemotherapy. However, after azacitidine (AZA) and donor lymphocyte infusion therapy, his leukemic blasts did not decrease. INTERVENTIONS: Originally, we had planned to proceed with a 2nd allo-HSCT with RIC regimen that consisted of fludarabine, melphalan and fractionated GO (3 mg/m/dose) on day -21, -18, and -15. However, the patient developed appendicitis after the last dose of GO when his neutrophil was 0 cells/µl. Based on his medical acuity, we terminated the rest of the patients conditioning regimen and the patient did not receive any further chemotherapeutics. The patient was still infused with peripheral blood stem cells from the donor on day 0. OUTCOMES: His appendicitis was resolved by antibiotics without surgery. His AML has been in CR more than 18 months under AZA maintenance therapy. LESSONS: GO monotherapy could be a conditioning regimen of 2nd allo HSCT from the same donor as the first HSCT for relapsed AML patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Gemtuzumab/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Adulto , Humanos , Masculino , Recidiva , Transplante Homólogo
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