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1.
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
2.
Article in Chinese | WPRIM | ID: wpr-781497

ABSTRACT

OBJECTIVE@#To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients.@*METHODS@#The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed.@*RESULTS@#Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications.@*CONCLUSION@#For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

3.
Article in Chinese | WPRIM | ID: wpr-873286

ABSTRACT

Objective::To explore the effect of modified Qingyitang combined with continuous blood purification in the adjuvant treatment of severe acute pancreatitis (SAP) complicated with multiple organ dysfunction (MODS) caused by heat accumulation of viscera. Method::Totally 100 cases of patients of SAP complicated with MODS, who were diagnosed as heat accumulation of viscera by traditional Chinese medicine(TCM) and treated in ICU of the First Affiliated Hospital of Hunan University of Chinese Medicine during May 2015 and May 2019, were randomly divided into two groups, namely control group and observation group, with 50 cases in each group. The patients in control group were treated with fasting and abstinence, gastrointestinal decompression, inhibition of trypsin secretion, gastric mucosal protection, early jejunal nutrition, reduction of inflammatory reaction, continuous blood purification (CBP), mechanical ventilation and circulatory support. The patients in observation group were treated by nasojejunal tube according to syndrome differentiation in addition to routine comprehensive therapy. Modified Qingyitang was injected for 7 days. The remission time of abdominal pain and distention, the time of first exhaust and defecation, the time of ICU residence, the number of samples falling off, the cause of death and the number of cases were recorded. Relevant indexes were measured before treatment, on the 3rd and 7th day of treatment, including the evaluation indexes of pancreatitis: blood amylase (AMS), blood lipase (LPS), and modified computed tomography severity index (MCTSI), inflammatory response indexes were interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP). Organ function indexes included APACHE-Ⅱ, arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyltransferase (γ-GGT), urine volume, creatinine (CREA), urea nitrogen (UREA), glomerular filtration rate (GFR), creatine kinase (CK), creatine kinase isoenzymes (CKMB), lactate dehydrogenase (LDH), myoglobin (Mb). Tissue perfusion evaluation indexes included acute physiology and chronic health score, serum lactic acid (Lac) and central venous pressure (CVP). TCM treatment score was based on the syndrome score of acute pancreatitis with heat accumulation of viscera syndrome. Result::The total effective rate of TCM syndromes was 86.67%(39/45) in observation group and 73.91%(34/46) in control group (χ2 =13.524, P<0.01). On the 7th day of treatment, the symptoms and indicators of the two groups were improved. Compared with before treatment, AMS, LPS, IL-6, hs-CRP, MCTSI, APACHE-Ⅱ, Lac, CVP, PaO2, PaO2/FiO2, ALT and AST were improved on the 3rd and 7th day after treatment in observation group and control group. The levels of AMS, LPS, IL-6, hs-CRP, MCTSI, APACHE-Ⅱ, Lac, CVP, PaO2, PaO2/FiO2, ALT, AST, ALP, γ-GGT, urine volume were significantly improved (P<0.05). Compared with control group on the 3rd and 7th day, the levels of AMS, LPS, IL-6, hs-CRP, MCTSI, APACHE-Ⅱ, Lac, CVP, PaO2, PaO2/FiO2, ALT, AST, ALP, γ-GGT, urine volume were significantly improved (P<0.05). CREA, UREA, GFR, CK, CKMB, LDH and Mb were significantly improved (P<0.05). Compared with control group, the abdominal pain, abdominal distension relief time, first exhaust/defecation time, ICU stay time in observation group were significantly shortened (P<0.05), and the mortality rate in observation group was significantly reduced (P<0.05). Conclusion::Patients of SAP accompanied with MODS can be treated with blood purification combined with modified Qingyitang by promoting pancreas repair, inhibiting inflammation and improving organ function. It plays an important role in improving symptoms, alleviating TCM syndromes, delaying progression of disease, reducing hospital stay and reducing mortality.

4.
Article in Chinese | WPRIM | ID: wpr-818942

ABSTRACT

Objective To evaluate the potential risk of schistosomiasis transmission so as to provide the evidence for formulating the control strategy. Methods Two villages were selected as the investigated sites in Chuxiong City and the risk of schistosomiasis transmission was evaluated by reviewing the data of schistosomiasis epidemic situation and prevention and control work, and carrying out the field survey for Oncomelania hupensis snail status, wild faeces, and schistosome infection of the population from 2015 to 2017. Results There was 1.49 hm2 area of snail habitats, with an average density of 0.54 snails/0.1 m2. The occurrence rate of frames with snails was 5.41%. No schistosome-infected snails were found. The positive rate of schistosomiasis serological tests of the residents was 3.36%, but the stool examination positive cases were not found. A total of 58 wild faeces samples were collected but no schistosome infested cases were found. The risk levels of schistosomiasis transmission in both villages were Grade III. Conclusions Although Chuxiong City has been in a low risk state of schistosomiasis transmission, the density of snails is still high, and there is a risk of infection source importation. In the future, the infection source control and snail control should be strengthened.

5.
Article in Chinese | WPRIM | ID: wpr-818490

ABSTRACT

Objective To evaluate the potential risk of schistosomiasis transmission so as to provide the evidence for formulating the control strategy. Methods Two villages were selected as the investigated sites in Chuxiong City and the risk of schistosomiasis transmission was evaluated by reviewing the data of schistosomiasis epidemic situation and prevention and control work, and carrying out the field survey for Oncomelania hupensis snail status, wild faeces, and schistosome infection of the population from 2015 to 2017. Results There was 1.49 hm2 area of snail habitats, with an average density of 0.54 snails/0.1 m2. The occurrence rate of frames with snails was 5.41%. No schistosome-infected snails were found. The positive rate of schistosomiasis serological tests of the residents was 3.36%, but the stool examination positive cases were not found. A total of 58 wild faeces samples were collected but no schistosome infested cases were found. The risk levels of schistosomiasis transmission in both villages were Grade III. Conclusions Although Chuxiong City has been in a low risk state of schistosomiasis transmission, the density of snails is still high, and there is a risk of infection source importation. In the future, the infection source control and snail control should be strengthened.

6.
Article in Chinese | WPRIM | ID: wpr-774310

ABSTRACT

OBJECTIVE@#To investigate the clinical biological characteristics and prognosis of the patients with mixed phenotype acute leukemia with t(9;22)(q34;q11.2) and/or BCRABL1 (Ph MPAL).@*METHODS@#The morphological, immunological, cytogenetic, and molecular features of 33 in patients with Ph MPAL were retrospectively analyzed in our center from June 2002 to June 2016 according to the scoring proposal of European Group for the Classification of Acute Leukemia(EGIL )1998 and WHO 2008 criteria. All the cases were either treated with acute lymphoblastic leukemia (ALL) induction regimen or combined chemotherapy regimens for both acute lymphoblastic and acute myeloid leukemia,part of which also received tyrosine kinase inhibitor(TKI) and 5 cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission.@*RESULTS@#Ph MPAL occurred predominantly in male patients (ratio of M/F was 1.75∶1), and a high WBC counts at diagnosis; the WBC count was higher than 30×10/L in 25 patients( 75.8% ), and appeared higher than 100 ×10/L in 13 patients ( 39.4%). Among all the 33 PhMPAL patients, 32 (97.0%) had a myeloid / B-lymphoid (M/B) phenotype, and 1 case(3.0%) had a myeloid/ B-lymphoid/ T-lymphoid/ (M/B/T) phenotype. There was no patients displayed myeloid / T-lymphoid (M/T) or B-lymphoid/ T-lymphoid/ (B/T) phenotype. 19 of all cases(57.6%) met the diagnosis criteria of PhMPAL based on EGIL 1998 criteria, while the remaining 14 cases can be diagnosed as Ph MPAL by WHO 2008 classification,but excluded as PhMAPL by EGIL 1998.Karyotype analysis was successfully performed in 31 cases, and out of them 13 (41.9%) had a sole Ph chromosome, 10 (32.3%) had additional chromosome aberration and Ph chromosome was not found in 8 cases (25.8%) .In 31 patients the fusion gene BCR/ABL (P190、P210) was detected,including 17 (54.8%) cases with the p190 BCR/ABL transcript, 8 (25.8%) cases with the p210 BCR/ABL transcript, 4 (12.9%) expressing both transcripts and 2 (6.5%) without any one of these 2 transcripts. 24 out of 33 patients (77.4%) achieved complete remission after induction therapy. The median time achieving CR was 43(26-98)days. The CR rate of patients treated with and without imatinib after the first inducion treatment was 81.3% and 46.7%,respectively (P0.05). Within the 17 patients treated with imatinib at induction stage,2 of which became BCR/ABLnegative.At consolidation chemotherapy stage, 9 out of 16 patients became BCR/ABL negative, including 3 patients already subjected to HSCT. The median time reached to BCR/ABL negative was 2.87(1.13-9.20)months.@*CONCLUSION@#Ph MPAL is more common in male, and inclined to high WBC counts at diagnosis. Myeloid/B lymphoid phenotype is more common, and the prognosis of patients with PhMPAL is poor. Imatinib and allogeneic hematopoietic stem cell transplantation may improve survival of patients with PhMPAL.


Subject(s)
Acute Disease , Fusion Proteins, bcr-abl , Humans , Leukemia , Male , Phenotype , Retrospective Studies
7.
Article in Chinese | WPRIM | ID: wpr-771906

ABSTRACT

OBJECTIVE@#To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1).@*METHODS@#The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed.@*RESULTS@#In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188);RFS (62.5% vs 38.9%) (P=0.166).@*CONCLUSION@#Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.


Subject(s)
Adult , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 19 , Homeodomain Proteins , Genetics , Humans , Immunophenotyping , Oncogene Proteins, Fusion , Genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Therapeutics , Recurrence , Remission Induction
8.
Journal of Experimental Hematology ; (6): 1589-1597, 2018.
Article in Chinese | WPRIM | ID: wpr-773051

ABSTRACT

OBJECTIVE@#To screen the differentially expressed proteins at the early stage of K562 cells treated with meisoindigo by using tandem mass tags (TMT)-based proteomics technology, and to explore the mechanism for meisoindigo-inducing apoptosis.@*METHODS@#The half inhibitory concentration (IC) of mesoindigo on K562 cells was determined by CCK8. The flow cytometry was used to assay the apoptosis of K562 cells treated by meisoindigo or DMSO. Total proteins were extracted from the cells treated with 0.2% DMSO (control) or 20 μmol/L meisoindigo (Test) for 2 hours. Then, the TMT-labeling HPLC-MS/MS was used to identify and quantify the peptides and their abundance, all the tests were repeated for 3 times. The Mascot software was used to identify the proteins; the GO annotations, enrichment and cluster analysis were used to analyze the differentially expressed proteins.@*RESULTS@#Meisoindigo-induced K562 cell apoptosis in a dose-dependent manner (r=0.98), 5 544 proteins were identified, 4792 of which were quantified. The protein with expression difference>1.5-folds in Test group accoanted for 8, out of which the expression of 4 proteins were up-regulated and 4 were down-regulated. The differentially expressed proteins mainly associated with reactive oxygen species (ROS).@*CONCLUSION@#Several proteins including DDIT4 were found to have dramatic changes in the early stage of K562 cells treated with meisoindigo by using quantitative proteomics technology. The ROS metabolic process may play important roles in meisoindigo-inducing apoptosis of K562 cells.


Subject(s)
Apoptosis , Humans , Indoles , K562 Cells , Proteomics , Tandem Mass Spectrometry
9.
Article in Chinese | WPRIM | ID: wpr-690930

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of serum procalcitonin(PCT) levels for predicting the outcome of bacteria bloodstream infection in acute leukemia patients.</p><p><b>METHODS</b>Clinical data from 236 patients with acute leukemia accompanied by bacterial bloodstream infection during July 2014 to November 2017 were retrospectively analyzed, 236 patients were divided into 5 groups (<0.05 ng/ml, 0.05- <0.5 ng/ml, 0.5- <2.0 ng/ml, 2.0- <10.0 ng/ml and >10.0 ng/ml) according to PCT concentrations.</p><p><b>RESULTS</b>The median age of patients was 40(13-73) years old. The male 123 cases(52.1%) and female 113 cases(47.9%) in 236 patients. The incidence of infection-related dealth in 5 groups was 0%, 1.4%, 13.8%, 25.0% and 33.3%, respectively; the incidence of septic shock and other serious complications in 5 groups was 0%, 2.1%, 13.8%, 25.0%, 33.3% and 6.4%, 7.0%, 24.1%, 41.7%, 50.0%, respectively, showing the concentration dependent manner and statistically significant difference (u=2127, P=0.000; u=2234, P=0.000; u=4102, P=0.000). Further analysis showed that with the increase of PCT concentration, the cumulative incidence of septic shock, infection-related death and other serious complications was gradually increased with statistically significance (HR=2.887, P=0.000, 95%CI:1.960-4.260; HR=3.158, P=0.000, 95%CI: 2.100-4.740; HR=2.158, P=0.000, 95%CI:1.550-3.000) respectively. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death (HR=2.517, P=0.000, 95%CI: 1.520-4.168; HR=2.881, P=0.000, 95%CI: 1.692-4.904)respectively.</p><p><b>CONCLUSION</b>Serum procalcitonin level positively correlates with the incidence of serious bacteria bloodstream infection complications in the patients with acute leukemia. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death, indicating that procalcitonin may be an important prognostic factor for infection outcome in acute leukemia patients with bacteremia.</p>


Subject(s)
Adolescent , Adult , Aged , Bacteremia , Biomarkers , C-Reactive Protein , Calcitonin , Calcitonin Gene-Related Peptide , Female , Humans , Male , Middle Aged , Protein Precursors , Retrospective Studies , Young Adult
10.
Journal of Experimental Hematology ; (6): 1269-1274, 2018.
Article in Chinese | WPRIM | ID: wpr-689492

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>Clinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent. The incidences of IPA and systemic antifungal treatment during induction chemotherapy were analyzed for both groups.</p><p><b>RESULTS</b>Among 102 enrolled cases, 42 cases received voriconazole and other 60 received posaconazole as primary prophylaxis. IPA occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred in 4 cases of posaconazose group, and all were possible cases. The incidence of IPA during remission-induction chemotherapy in variconazole group equaled to posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in voriconazole group and 4 cases in posaconazole group received intravenous anti aspergillosis drugs preemptive treatment, and no significant difference of prophylactic success rate was observed between two groups (88.1% vs. 86.7%) (P=0.831). Visual disturbance was the most common adverse event occurred in voriconazole group, but no significant differences of incidences of other adverse effects were observed when compared with posaconazole group.</p><p><b>CONCLUSION</b>According to similar prophylactic effect with posaconazole, voriconazole appears to be a good alternative for primary prophylaxis of IPA during remission-induction chemotherapy in AML patients.</p>

11.
Journal of Experimental Hematology ; (6): 1621-1626, 2017.
Article in Chinese | WPRIM | ID: wpr-278773

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effect of c-FLIP expression on drug resistance of Kasumi-1 leukemia cells and its mechanisms.</p><p><b>METHODS</b>Tet-on inducible system was used to construct the conditional expression vector of c-FLIP by cloning the c-FLIP gene into lentivirus vector pLVX-Tight-Puro, then the Kasumi-1 cells were transfected with lentivirus pLVX-Tight-Puro-c-FLIP. The expression of c-FLIP was induced by doxycycline(Dox) for different time and doses, and verified by qRT-PCR and Western blot. On the basis of the overexpression of c-FLIP, the Kasumi-1-c-FLIP cells were treated with CH11 and PB in order to induce apoptosis, and the Giemsa staining was used to show the apoptotic cell morphology.</p><p><b>RESULTS</b>qRT-PCR and Western blot showed the overexpression of c-FLIP, the CH11 and PB can induce Kasumi-1 cell apoptosis, while the c-FLIP overexpression weakened this effects. Western blot showed that the c-FLIP blocked the caspase-8 activation.</p><p><b>CONCLUSION</b>The overexpression of c-FLIP inhibits the apoptosis caused by CH11 and PB, and leads to drug resistance in leukemia cells.</p>

12.
Journal of Experimental Hematology ; (6): 1615-1621, 2016.
Article in Chinese | WPRIM | ID: wpr-332640

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the influence of FLT3-ITD mutation on long term survival of newly diagnosed patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Long term survival of 170 newly diagnosed APL patients was retrospective analyzed. Mutation rate of FLT3-ITD was assayed, and its influence on disease-free survival(DFS) or overall survival (OS) was analyzed.</p><p><b>RESULTS</b>The mutation rate of FLT3-ITD in newly diagnosed patients with APL was 14.1%. WBC count at diagnosis was higer in FLT3-ITD positive group than that in negative group, and the mutation rate of FLT3-ITD was highest in high risk group. Induction death rate in FLT3-ITD positive and negative group were 12.5% and 2.9%, respectively (P=0.031). Complete remission(CR) rate in 2 groups were 83.3% and 97.1%(P=0.004). The 5-year OS rates in 2 groups were 87.5±6.8% and 90.6±2.6% (P=0.740). The 5-year DFS in 2 groups were 82.8±9.1% and 83.6±3.4%(P=0.928).</p><p><b>CONCLUSION</b>FLT3-ITD mutation is related with high peripheral white blood cell count in APL, the APL with FLT3-ITD mutation has higher induction death rate and lower CR rate than those in that without FLT3-ITD mutation, but FLT3-ITD mutation did not affect on long term DFS and OS.</p>

13.
Journal of Experimental Hematology ; (6): 1702-1708, 2015.
Article in Chinese | WPRIM | ID: wpr-272535

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of TBLR1-RARα on the differentiation induction of leukemia cell line K562 cells into erythroid lineage and to investigate its related mechanisms.</p><p><b>METHODS</b>Tet-Off inducible system was used to construct the conditional expression vector of TBLR1-RARα fusion gene by cloning the TBLR1-RARα fragment into lentivirus vector pLVX-Tight-Puro, the expression of TBLR1-RARα fusion gene was induced by doxycycline (Dox). Then, K562 cells were transfected with lentivirus pLVX-Tight-Puro-TBLR1-RARα-flag, and the expression of fusion proteins was verified by Western blot. After treatment of K562 with all-trans retinoid acid (ATRA), real time RT-PCR was performed to test the expression of erythroid differentiation-related CD71 and α, ε, γ-globins gene. Flow cytometry was used also to analyze the expression of erythroid differentiation markers CD71 and CD235a. Benzidine staining was used to detect the production of hemoglobin in K562 cells.</p><p><b>RESULTS</b>qRT-RCR showed that ATRA could increase the expression level of CD71 and α, ε, γ-globin genes when TBLR1-RARα was expressed. After treatment of ATRA, the proportion of CD71(+) cells detected by the flow cytometry also increased. Benzidine staining showed that ATRA could induce hemoglobin production in K562 cells with TBLR1-RARα fusion gene expression.</p><p><b>CONCLUSION</b>The expression of TBLR1-RARα fusion gene contribute to ATRA-inducing differentiation of K562 cells into erythroid lineage.</p>


Subject(s)
Cell Differentiation , Erythrocytes , Hemoglobins , Humans , K562 Cells , Nuclear Proteins , Receptors, Cytoplasmic and Nuclear , Receptors, Retinoic Acid , Repressor Proteins , Retinoic Acid Receptor alpha , gamma-Globins
14.
Article in Chinese | WPRIM | ID: wpr-259640

ABSTRACT

<p><b>OBJECTIVE</b>This studay was aimed to explore the incidence and risk factors of tumor lysis syndrome (TLS) in patients with acute leukemia.</p><p><b>METHODS</b>A tatol of 380 patients who were newly diagnosed as acute leukemia and received combination chemotherapy were retrospectively analyzed. The TLS was diagnosed according to criteria of Cario and Bioshop, the risk factors were evaluated on basis of examination results.</p><p><b>RESULTS</b>The tumor lysis syndrome occurred in 20.8% (79/380) of patients, out of them the clinical TLS was 0.5% (2/380), laboratorial TLS was 20.3% (77/380). The unvariate analysis showed that male, high WBC count, hepatomegaly, splenomegaly, lympha-denoctasis, elevated AST, high creatinine, high uric acid level, high serum lactate dehydrogenase (LDH) level, or renal insufficiency were independent risk factors for TLS.</p><p><b>CONCLUSION</b>The TLS is a clinically common complication in patients with leukemia, especially during induction chemotherapy, therefore, for AL patients with high risk factors the TLS should be closely monitored, prevented and given better therapy.</p>


Subject(s)
Acute Disease , Humans , Incidence , Induction Chemotherapy , Leukemia , Male , Renal Insufficiency , Retrospective Studies , Risk Factors , Tumor Lysis Syndrome
15.
Article in Chinese | WPRIM | ID: wpr-259595

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the incidence of karyotypes and gene mutations for elder acute myeloid leukemia and to explore the relationship between each other.</p><p><b>METHODS</b>Clinical data and bone marrow samples of elder AML patients were collected. Karyotype and gene mutation (FLT3, NPM1, C-Kit, CEBPα, DNMT3A) test were performed, characteristics of karyotypes and gene mutations were analysed.</p><p><b>RESULTS</b>The incidence of better risk karyotype was 16.6%, in which the incidences of t(15;17), t(8;21) and inv (16)/t(16;16) were 3.90%, 10.73%, and 1.95% respectively; the incidence of intermediate risk karyotype was 72.2%, in which the incidence of normal karyotype was 57.86%; the incidence of poor risk karyotype was 11.20%, in which the incidence of of MLL/11q23, complex karyotype and monosomal karyotype were 1.95%, 6.34%, 5.85% respectively; the incidences of FLT3, NPM1, C-Kit, CEBPα, DNMT3A mutation were 12.57%, 22.06%, 2.16%, 14.71%, 15.71% respectively. Compared with patients older than 60 years, patients with age of 55-60 years were with less complex karyotype (1.09% vs 10.62%)(P=0.003) and monosomal karyotype (2.17% vs 8.85%)(P=0.032), and more t(8;21)(17.39% vs 5.31%)(P=0.008) and inv (16)/t(16;16)(4.35% vs 0.00%)(P=0.045).</p><p><b>CONCLUSION</b>For older AML patients, great difference in the distribution of karyotyes was found between the patients older than 60 years and patients with age of 55-60 years, while no such characteristics was found for gene mutations. Good elucidation of karyotypes and gene mutations are key for the treatment of older acute myeloid leukemia patients.</p>


Subject(s)
Humans , Incidence , Karyotype , Karyotyping , Middle Aged , Mutation , Proto-Oncogene Proteins c-kit
16.
Article in Chinese | WPRIM | ID: wpr-259578

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of MAC regimen in the treatment of acute myeloid leukemia(AML) patients older than 55 years.</p><p><b>METHODS</b>A total of 33 relapsed or non-remission AML patients older than 55 years were enrolled in this research. MAC regimen was given as the salvage treatment. Complete remission rate(CR), partial remission rate(PR), overall survival(OS), relapse-free survival(RFS) and adverse effect were analysed.</p><p><b>RESULTS</b>CR rate after the salvage therapy with MAC was 51.1%, partial remission (PR) rate was 6.1%, the overall response rate (ORR) was 57.6%, the median OS was 8 months (1.0-66.0 months), the median relapse-free survival (RFS) was 10.1 months (2.3-40.4 months). Mortality related with salvage treatment in 30 days was 9.1%. Low incidence of severe organ damage were found.</p><p><b>CONCLUSION</b>MAC can be used as a relative effective and safe regimen for the salvage treatment of the older AML patients.</p>


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Chlorambucil , Cytarabine , Dactinomycin , Humans , Leukemia, Myeloid, Acute , Methotrexate , Middle Aged , Recurrence , Remission Induction , Salvage Therapy
17.
Article in Chinese | WPRIM | ID: wpr-302369

ABSTRACT

Ribosomal protein S27a (RPS27a) can perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The RPS27a gene has been reported to be over-expressed in breast fibroadenomas, colorectal and renal cancers, advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. This study was purposed to explore the function of RPS27a in CML-erythroleukemia cell line K562 cells. RPS27a was silenced by short hairpin RNA (shRNA) in K562 cells. Furthermore, the proliferation changes of K562 cells was detected by MTT method after silencing the RPS27a with suberoylanilide hydroxamic acid (SAHA), then the IC50 of K562-sh1/sh2 and K562-scr cells to SAHA was measured. The results indicated that compared with K562-scr cells, the IC50 of K562-sh1/sh2 to SAHA at 24 h and 48 h decreased (P < 0.01); RPS27a silence significantly increased the percentage of apoptotic K562-sh1/sh2 cells after incubation with 1 µmol/L, 2 µmol/L and 5 µmol/L SAHA for 24 h and 48 h as compared with that of K562-scr cells (P < 0.01). K562-sh1, K562-sh2 and K562-scr cells after incubation with or without 2 µmol/L SAHA for 48 h presented apoptosis features: i. e. chromatin condensation, nucleic fragmentation and apoptotic body formation. It is concluded that RPS27a can inhibit the apoptosis of K562 cells and RPS27a silence can potentiate sensitivity of K562 cells to SAHA.


Subject(s)
Apoptosis , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Gene Silencing , Humans , Hydroxamic Acids , Pharmacology , K562 Cells , RNA, Small Interfering , Genetics , Ribosomal Proteins , Genetics , Metabolism
18.
Article in Chinese | WPRIM | ID: wpr-349661

ABSTRACT

This study was aimed to explore the role and mechanism of IFN-γ in the regulation of hemopoiesis in mice. Murine IFN-γ fragment was amplified from murine splenic cells with RT-PCR and plasmid pCDH1-mIFN-γ-EF1-copGFP (pCDH-mIFN-γ-GFP) was constructed. Plasmids pCDH-mIFN-γ-GFP and pCDH1-EF1-copGFP (pCDH-GFP) together with packaging plasmids pPACK-A, pPACK-B and pPACK-C were respectively transfected into 293T cells by using a method of calcium phosphate precipitation to produce lentivirus. Bone marrow mononuclear cells (BMMNC) from male C57BL/6J mice were transfected with the lentiviral vector pCDH expressing mIFN-γ and green fluorescent protein (GFP). The cells were cultured in M3434 semi-solid medium for colony formation assay and transplanted into lethally-irradiated mice through caudal vein injection, and the peripheral blood cell counts and GFP were monitored regularly after transplantation. The results showed that lentiviral vector pCDH-mIFN-γ-GFP was constructed successfully and 293T cells transfected with mIFN-γ secreted mIFN-γ. Transfection of mIFN-γ into BMMNC decreased colony formation, colony number of the mIFN-γ group was significantly less than that of the control group. The recovering of circulating blood cell parameters in mIFN-γ transplantation group was significantly later than control group. GFP positive cells could be detected in the peripheral blood at 8 weeks after transplantation. It is concluded that mIFN-γ may inhibit the colony-forming capacity of transduced BMMNC and delay the hematopoietic reconstitution.


Subject(s)
Animals , Bone Marrow Cells , Cell Biology , Cell Line , Genetic Vectors , Hematopoiesis , Genetics , Interferon-gamma , Genetics , Pharmacology , Lentivirus , Genetics , Male , Mice , Mice, Inbred C57BL , Plasmids , Transfection
19.
Article in Chinese | WPRIM | ID: wpr-264959

ABSTRACT

The purpose of this study was to investigate the clinical characteristics of newly diagnosed acute myeloid leukemia (AML) patients with NPM1 mutation in exon 12 and to explore the relationship between NPM1 mutation and FLT3-ITD, IDH1 mutation. The AML clinical data and bone marrow samples of patients were collected. The diagnosis and classification were based on WHO criteria. The genomic DNA was extracted and NPM1 mutation was detected by sequencing after PCR. The specimens of 389 AML patients were tested. The results showed that the NPM1 mutation was found in 14.1% samples (55/389). The incidence of FLT3-ITD mutation was 14.7% (57/389) . The incidence of IDH1 mutation was 6.4% (25/389) . NPM1 mutation was not detected in AML with AML1-ETO, PML-RARA or CBF-MYH11 fusion genes. The incidences of FLT3-ITD and IDH1 mutation were 29.1% and 12.7% respectively in AML with NPM1 mutation. The incidences of FLT3-ITD and IDH1 mutation were 12.3% and 5.4% respectively in AML without NPM1 mutation. The incidences of FLT3-ITD and IDH1 mutation were significantly higher in AML with NPM1 mutation than that in AML without NPM1 mutation. The incidence of NPM1 mutation in normal karyotype AML was 26.5% (35/132) which significantly higher than that in other AML. The AML with NPM1 mutation characterized by older age, high platelet number, higher incidence in AML-M5, lower CD34 positive cells, more possible co-existence with FLT3-ITD and IDH1 mutation and other clinical features. The complete remission rate after one cycle of induction chemotherapy was 69.8% in AML without NPM1 mutation. The complete remission rate after one cycle of induction chemotherapy was 72.2% in AML with NPM1 mutation, there was no significant difference between them (P = 0.07). It is concluded that AML with NPM1 mutation has distinct clinical features. NPM1 mutation can co-exists with FLT3-ITD and IDH1 mutation, but not with AML1-ETO, PML-RARA or CBF-MYH11 fusion genes.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Isocitrate Dehydrogenase , Genetics , Leukemia, Myeloid, Acute , Diagnosis , Genetics , Male , Middle Aged , Mutation , Nuclear Proteins , Genetics , Prognosis , Young Adult , fms-Like Tyrosine Kinase 3 , Genetics
20.
Chinese Journal of Hematology ; (12): 93-97, 2013.
Article in Chinese | WPRIM | ID: wpr-323436

ABSTRACT

<p><b>OBJECTIVE</b>To compare the efficacy and safety of dasatinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP).</p><p><b>METHODS</b>37 CML-CP patients were randomized to receive dasatinib 100 mg orally daily or imatinib 400 mg orally daily. The efficacy and safety data were collected and compared.</p><p><b>RESULTS</b>Of 37 CML-CP patients, 18 received dasatinib and 19 received imatinib. The both of median duration of drug therapy and follow-up were 38 months. (1) The rate of complete cytogenetic response (CCyR) at 12 months was higher in dasatinib group than in imatinib group (89% vs 68%), but there was no significantly statistic significance between two groups (P = 0.232). The cumulative CCyR rate by 36 months was 89% in both arms. The major molecular response (MMR) at 18 months was 76% in dasatinib arm, being significantly higher than that in imatinib arm (37%) (P = 0.017). The cumulative MMR rate by 36 months was 82% versus 68% in dasatinib or imatinib (P = 0.694). The median time to CCyR and MMR was significantly faster for dasatinib than for imatinib (3 months vs. 6 months, and 14 months vs. 34 months, respectively). (2) The drug-related adverse events were mostly grade 1/2 and were well-tolerated. Increase of serum glutamic pyruvic transaminase, pleural effusion and thrombocytopenia were more common in dasatinib arm, while hypophosphatemia, edema and neutropenia were more common in imatinib arm.</p><p><b>CONCLUSION</b>Dasatinib is an effective and safe therapy option and can be used as first-line therapy for newly diagnosed CML-CP patients.</p>


Subject(s)
Adult , Aged , Benzamides , Therapeutic Uses , Dasatinib , Female , Humans , Imatinib Mesylate , Leukemia, Myeloid, Chronic-Phase , Drug Therapy , Male , Middle Aged , Piperazines , Therapeutic Uses , Pyrimidines , Therapeutic Uses , Survival Rate , Thiazoles , Therapeutic Uses , Treatment Outcome , Young Adult
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