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microRNA (miRNA) refers to small (19-25 nt) single-stranded noncoding RNA molecules that work as post-transcriptional regulator for gene expression by binding to 3' untranslated regions of target mRNA,thus inducing its digestion,degradation and translational repression.Many studies have confirmed that dysregulation of miRNA expression can cause disruption of the hematopoietic system and contribute to leukemogenesis by regulating the expression of some oncogenes and anti-oncogenes.The unique miRNA expression profiles associated with cytogenetic aberrations and mutational status of protein-coding genes may reveal insight into the biology of these leukemia types.This review discussed the latest studies on miRNA expression in different cytogenetic and molecular subtypes of acute myelocytic leukemia and acute lymphoblastic leukemia.
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Objective To investigate the effect of astragalus polysaccharide (AP) on proliferation and apoptosis of human acute myelocytic leukemia cell line KG-1a and the underlying mechanisms.Methods Human acute myelocytic leukemia cell line KG-la was cultured under 37 ℃ and 5 ％ C02,when appropriate cell passage and cryopreservation were performed.After treatment for 48 h with different concentrations of AP,the proliferative activity and apoptosis rate of KG-1a cells were examined by CCK-8 assay and flow cytometry,respectively.The expressions of p-Akt and bcl-2 protein in AP-treated KG-1a cells were evaluated by Western blot.The expression of PTEN mRNA by quantified real-time PCR.Results The proliferative activity of KG-la cell was obviously suppressed by AP treatment,and the inhibition rate increased in a dosedependent manner.The flow cytometry showed that,compared with the control group,the apoptosis rates of KG-1a cells were significantly increased after treatment with AP for 48 h.The early apoptosis rates were (1.98±0.16) ％,(12.60±0.48) ％,(16.31±0.73) ％,the late apoptotic rates were (3.11±0.19) ％,(17.17±1.40) ％,(21.17 ± 0.81)％,the differences were statistically significant (P ＜ 0.05).Western blot showed that the expressions of p-Akt and bcl-2 protein in KG-1a cells decreased significantly after treatment with AP (P ＜ 0.05).In contrast,the mRNA level of PTEN increased (P ＜0.05),which was shown by real-time PCR.Conclusion AP could repress cellular proliferation activity of KG-1a cells,which could be attributed to inhibition of PTEN-PI3K-Akt signaling pathway.
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Acute myeloid leukemia (AML) is the major topic in American Society Hematology (ASH)Annual Meeting and Exposition. There were 887 scientific articles on AML in the 53rd ASH Annual Meeting and Exposition in 2011,in which many studies focused on clinics.Here is introduction of o.ptimized regimens for AML and elderly AML,as well as targeted therapy for AML presented in the meeting.
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Objective To study the significance of morphologic, immunophenotype, cytogenetic features, molecular biology (MICM) and prognosis of t (8;21) acute myeloid leukemia (AML) patients.Methods Morphological, FAB subtypes, flow cytometric immunophenotyping, G-binding technique and RTPCR were performed in 70 AML patients with t (8;21) and AML1-ETO fusion transcripts as compared with normal karyotype 70 AML patients. Results In 70 AML patients with t(8;21), 1 case of M1, 64 cases of M2, 3cases of M4 and 2 cases of ambiguity AL according to FAB classification. The CD13, CD33, CD34 and CD117expression were higher, meanwhile CD19 was positive in 40 %, CD15 was 11%, CD11b was 10 % and CD7 was 7 %. Cytogenetically, 50 % cases had additional chromosomal abnormalities, and main associated recurrent additional abnormalities were loss of a sex chromosome, 9q- and hyperdiploid. AML1/ETO fusion gene transcripts were detected in all 70 AML patients with t(8;21) by RT-PCR. CR rate of t(8;21) AML with CD19were 72 %, t(8;21) AML with CD19 and CD7 were 0; in normal karyotype AML were 31%. Conclusion The t(8;21) is the characteristic chromosome abnormality of M2. In the t(8;21), CD19, CD34 and CD117 expression are high, while CD7 are low. These antigen expression in t(8;21) AML closely correlated with karyotype. CD19 is a marker of good prognosis, but CD7 is a marker of low CR.
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Acute myeloid leukemia (AML) is a heterogenous disorder disease, about 40 %-49 % of the adult AML and 25 % of children had normal karyotype AML, and usually categorized as an intermediaterisk group, but for acquired genetic change, such as mutations of FLT3, NPM1, CEBPα, MLL, and KIT as well as alterations in expression levels of BAALC, MN1, ERG, and EVI1, leading to significant heterogeneity for the prognosis of this group. In this report, prognostic genetic findings in normal karyotypical AML and discuss their clinical implications was reviewed.
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Objective The current study was designed to investigate the inhibitive effect of celastrol on the proliferation of acute myelogenous leukemia (AML) cells. Methods The effect of celastrol on AML cells in vitro was examined by MTT assay and flow cytometry (FCM). Results After the AML primary cells were treated with different concentrations of celastrol, the results were analyzed by MTT. The growth of the cells were significantly inhibited compared with the control group (P ＜0.01). The results detected by FCM showed that the apoptosis was seen after treated with celastrol with different concentration for different times.The apoptotic rates were significantly higher than that in the control group with statistical significance (P＜ 0.01).Conclusion Celastrol could inhibit the proliferation of AML cells in vitro, which may be associated with inducing cell apoptosis.
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Objective To explore the cytogenetic characteristics of acute myeloid leukemia(AML) patients.Methods The karyotype analysis was performed in 178 AML using the short-term culture of bone marrow cell and G-banding technique.Results Among the 178 patients,171 had enough metaphases for analysis and 128(74.9%)had clonal karyotypic abnormalities.Twenty-seven patients were secondary to myelodysplastic syndrome (MDS-AML),with 25 (92.6%) patients carrying clonal karyotypic abnormalities.Among the remaining 144 patients of de novo AML,103(71.5%)had clonal karyotypic abnormalities.The rate of abnormal clonal karyotype was higher in MDS-AML than that of de novo AML (P=0.021).Among the 171 patients,41(24.0%)were in favorable risk group,80(46.8%)in intermediate risk group and 50(29.2%)in adverse risk group.t(15;17)was the most common chromosomal aberration.The maiority intermediate risk chromosomal aberration was;normal karyotype.The most common cytogenetic abnormality among adverse group was a complex karyotype.Adverse cytogenetic aberrations,such as -5/5q-,-7/7q-,frequently occurred in conjunction with one another as part of a complex karyotype.Totally 75 patients were 60 years or older,among them,16.0%were in favorable risk group,48.0%in intermediate risk group and 36.0%in adverse risk group.Among 96 younger patients,30.2%were in favorable risk group.45.8%in intermediate risk group and 24.0%in adverse risk group.The rate of favorable risk chromosomal aberration was lower in elder patients than in younger(P=0.03 1).The rate of adverse risk chromosomal aberration and the rate of monosomal karyotype were higher in MDSAML than in de novo AML patients(P<0.001).Conclusions The most common favorable,intermediate and adverse chromosomal aberrations were t(15;17),normal karyotype and complex karyotype respectively.The karyotype was poor in MDS-AML and elder AML patients.
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Objective To explore the efficacy and safety of HAA regimen (homoharringtonine,cytarabine and aclarubicin) in the treatment of 150 newly diagnosed adult acute myeloid leukemia (AML).Methods All patients entered the study from May 1999 to June 2008 were treated with HAA regimen. Coxsurvival analysis was used to estimate the survival rate and differences between M1/M2 and M4/M5 were compared with 2-sided log-rank test. Results Out of the 150 patients, 121 (81%) achieved complete remission (CR). After the first course, CR rate was 68%. The CR rates of 97%, 84% and 38% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. For the patients with CR, the median follow-up time was 16.5 ( 1.5-100.5 ) months, and the estimated 3-year survival rate was 45%. The estimated 3-year relapse free survival rate was 52% for the 121 patients with CR.Conclusions HAA regimen may be an efficacious and safe regimen with a good toleration in the induction therapy for newly diagnosed AML, and a high CR rate could be achieved with only one or two courses.
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Objective To isolate and identify leukemia stem cells from acute myeloid leukemia patients for further research. Methods By Ficoll density gradient centrifugation, mononuclear cells were firstly separated from bone marrow of patients. According to specific surface markers, CD+34 CD+123 of leukemic stem cells were sorted by flow cytometer. Their ability of self-renewal and differentiation were evaluated by colony formation and cobblestone forming ability. At the same time, the purity and cell morphology of CD+34 CD+123 cells was analysed. Results Comparared with total mononuclear cells, the proportion of the CD+34 CD+123 cells after sorting was 10.7 %, and these cells showed the ability of colony forming and cobblestone forming, and the purity proportion of CD+34 CD+123 cells was 62.1%. Conclusion The leukemia stem cells were isolated successfully and could be used in further study.
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Objective To investigate the clinical features, therapy and prognosis of elderly patients with newly diagnosed acute promyelocytic leukemia (APL). Methods The clinical features of 21 elderly patients and 89 patients aged ＜60 with newly diagnosed APL were retrospectively analyzed. Additionally,elderly patients were divided into different groups according to the count of white blood cell (WBC). Results There were no significant differences between elderly patients and patients aged ＜60 in the aspect of sex (male/female: 11/10 vs 47/42), WBC count (high initial WBC: 23.8 % vs 16.9 %), the percentage of bone marrow blasts plus promyelocytes (0.83±0.11 vs 0.83±0.12), complete remission (CR) rate (71.4 % vs 84.3 %),the time of CR occurrence (35.7±10.1 vs 39.1±13.5), the occurrence of retinoic acid syndrome(RAS) (14.3 % vs 22.5 %), disseminated intravascular coagulation (DIC) (52.4 % vs 34.8 %) as well as 2 years overall survival rate (72.7 % vs 80.0 %) (P ＞0.05). Of the 21 elderly patients who received inductive treatment, 5 with high initial WBC and 16 without high initial WBC. The incidences of DIC, early death in high initial WBC group were 80 %, 60 % respectively, which were higher than the group without high initial WBC (43.8 %,18.8 % respectively), whereas CR rate for the group with high initial WBC (40.0 %) was lower than that for the group without high initial WBC (81.3 %). Conclusion Elderly patients with APL could have fine prognosis as well as patients aged ＜60. The results of inductive treatment of elderly patients in high initial WBC group were poor as compared with the group without high initial WBC.
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Objective To investigate the incidence and distribution of aberrational karyotype in acute myeloid leukemia (AML), and study the significance of the grouping by Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) in the prognosis of AML Methods The chromosome was prepared with brief culture of bone marrow, and the karyotype was analysed by G banding technique. All the patients were grouped according to the criterion of SWOG/ECOG, and the survival function of different groups was observed by the Kaplan-Meier method.Results 56 (67.47 %) out of 83 patients had clonal chromosome aberrations. Among those 56 patients, AML with translocation (15;17) and with translocation (8;21) presented in 30 patients(53.57 %), and the other kinds of aberrational karyotypes shared the left proportion. Among the 74 followed-up patients, 42 patients were dead. Among three groups with favorable, intermediate and adverse prognosis respectively, there is a significant difference (P 0.05). Conclusion Cytogenetic aberration is one of the important factors affecting the effect on prognosis. The criterion of SWOG/ECOG can predict prognosis objectively.
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One of the sub-types of acute myeloid leukemia(AML) characterized by the translocation of chromosome 8 to chromosome 21 and the expression of AML1-ET0 leukemia genesis fusion gene was proven to have better prognosis. Although remission rate has been improved by the combined chemotherapy primarily containing high dose cytarabine,it seems that target treatment with AML1-ET0 fusion gene/protein should finally cure this disease. In this article,we reviewed the relative studies and clinic target-treatment on AML1-ETO.
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FLT3, a tyrosine kinase receptor, is the most common mutation in AML and has two classes of mutations: internal tandem duplications in the juxtamembrane domain (FLT3-ITDs) and point mutations in the tyrosine kinase domain (FLT3-TKDs). AML patients with FLT3 mutations tend to have a poor prognosis. As an independent factor, the presences of FLT3 mutations play an important role in the origin and development of AML and have prognostic value. Molecular targeted therapy represents a novel and popular therapeutic approach in the world. In this review, we explain clinical value of the FLT3 mutations, mechanism and research progression of the FLT3 inhibitor;and discuss difficulties and perspectives in the research of the FLT3 inhibitor.
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Objective To observe the therapeutic effect and adverse effect for chemthrombocytopenic of rhIL-11 in chemotherapy for acute myeloid leukemia. Methods We adopted a randomized, blank-control, crossover trial of rhIL-11 in 16 newly diagnosed patients with acute myeloid leukemia. The treatment group were accepted chemotherapy by DA or TA. rhIL-11 (25μg·kg-1·d-1, subcutaneously) was administered from 24 h after chemotherapy and continued for seven to fourteen days. The changes of platelet counts were observed. Results The group by chemotherapy had higher platelet counts than control after rhIL-11 treatment and platelet transfusion frequency was reduced. The adverse effect of rhIL-11 was light, including fatigue, muscular soreness and low-grade fever. Conclusion rhIL-11 is safe and effective in reducing chemotherapy thrombocytopenia.
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Objective To explore in vitro effects and the mechanism for FLAG regimen compared with IA regimen in P-glycoprotein-positive and -negative acute myeloblastic leukemia(AML) cell lines. Methods The expression of P-glycoprotein in K562 and K562/A02 cells were analyzed by flow cytometry. The effects of FLAG and IA on the proliferation of K562 and K562/A02 cells were detected by MTT assay. The Ara-CTP and Ara-C levels in those cells were measured by HPLC,the gene expression of hENT1 in K562 and K562/A02 cells was detected by real-time PCR. Results The positive rates of P- glycoprotein were (1.32±0.24)% in K562 cell and (97.66±3.77)% in K562/A02 cell, respectively. The expression of P- glycoprotein had no change after treated with FLAG or IA. The cytotoxicity to K562 of IA was better than FLAG [(84.41±9.33) % v.s (73.17±13.20)%, P<0.05], and the cytotoxicity to K562/A02 of FLAG was better than IA [(70.55±11.32)% v.s (48.46±12.81)%, P<0.01]. Ara-C and Ara-CTP accumulation and hENT1 expression in AML cells treated with FLAG were higher than that treated with IA. Conclusion P-glycoprotein-positive AML cells are more sensitive to FLAG regimen than IA regimen. The biochemical modulation of Ara-CTP and Ara-C may be the major mechanism.
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Objective To evaluate the efficacy and toxicity for the protocol of low-dose harringtonine and cytarabine(HA regimen)in combination with granulocyte colony-stimulating factor(G-CSF)in elderly patients with acute myelogenous leukemia(AML).Methods Thirty-five AML patients were treated with HAG including low-dose chieved PR.The overall response rate was 83%.5 of 35(14%)was non-remiasion.Two patients died in the duration of treatment.The main complication of chemotherapy is myelosuppresion.Conclusion Low-dose HA regimen in combination with G-CSF is effective and safe in elderly patients with AML.
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As one of the cytokines which play important role in the regulation of immune system,such as activating and maintaining immune response and promoting lymphocyte development,interleukin-2 is secreted by activated T cell or NK cell and has been extensively applied to clinical therapy and laboratory research. This paper is maily about the anti-tumor mechanism of interleukin-2 and its application in the treatment of patients with acute myelogenous leukemia.
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Objective To investigate the clinical and biologic characteristics of acute myeloid leukemia (AML) with 6q deletions (6q-). Methods Two cases of with 6q deletions (6q-) were here described, and all the AML cases with 6q- found in the literature were reviewed. Results Two cases were diagnosed with AMLMt and AML-M2, respectively. Myloloid markers were positive on the leukemia cells in both cases, none of them expressing lymphocytic antigens. The karyotype of these patients were 46,XX,del(6)(q21q25),t(4; 7)(q10;q10)[3]/46,XX,del(6)(q21q25)[2]/46,XX[25], and 46,XX,del(6)(q23),t(7;11)(p15;p15)[5]/46,XX,t(7;11)' (p15;p15)[9]/46,XX [6]. Until now, 28 cases (including present 2 cases) of AML with 6q- have been documented in the world literature. Many of the AML patients with 6q -have additional chromosomal abnormalities. The breakpoints on 6q- were widely distributed from q12 to q27, mainly involved in the 6q21-23 region. Overall, the AML patients with 6q- were associated with an unfavorable clinical outcome, with a poor response to chemotherapy and a shorter duration. 6q-clone may itself confer a malignant clinical outcome. The 6q- found in some AML cases may associate with leukemogenesis via an activation of an oncogene other than myb or deletion of an antioncogene located in the long arm of chromosome 6. Conclusion Deletion of 6q is a very rare event in AML. AML with 6q- had distinct biologic features and a. poor clinical outcome.
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Objective The aim of the study was to explore the difference between the expression of CDg7 in peripheral blood and bone marrow on acute myeloid leukemia (AML n=30). Methods A flow cytometric quantitative analysis of expression levels for CD87 was performed on fresh blast cells in peripheral blood and bone marrow from patients with acute myeloid leukaemia using CD87, monoclonal antibodies. Analysis the difference between the expression of CD87 using matched t -test. Results The values of CD87 expression in bone marrow of 14 M5 cases are from 9.47 %～80.32 %, and from 11.49 %～87.46 % in peripheral blood. The values of CD87, expression in bone marrow of 8 M4 cases are from 14.27 %～46.28 %,and from 14.79 %～47.19 % in peripheral blood. The values of CD87 expression in bone marrow of 6 M2 cases are from 4.67 %～34.26 %, and from 8.96 %～39.78 % in peripheral blood. The values of CDs, expression in bone marrow of 2 MI cases are from 3.56 %～7.69 %, and from 5.21 %～8.96 % in peripheral blood.The expression of CD87 in peripheral blood and bone marrow from patients with acute myeloid leukaemia had statistical difference (t =3.13, P<0.05). Conclusion The levels of CD87 expression had difference between peripheral blood and bone marrow. The level in peripheral blood was higher than bone marrow. So when we performed quantitative analysis of expression levels for CD87, peripheral blood instead of bone marrow was commended.
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Objective: To study the mRNA expression in TGF-β1 signaling transduction pathways during the differentiation of acute promyelocytic leukemia (APL) induced by all-transretinoic acid (ATRA). Methods: The mRNA expressions of TGF-β1, TGF-βR I, TGF-βR II, Smad 2, Smad 3, Smad 4, and Smad 7 of human APL cell line NB4 were analyzed using a real-time fluorogentic quantitative-polymerase chain reaction (RFQ-PCR) assay after treatment with ATRA. The locations of PML-RARα fusion protein and Smad3 protein in NB4 cells were determined by confocal microscopy. Results: The mRNA expression levels of TGF-β1, TGF-βR I, TGF-βR II, Smad 2, Smad 3, Smad 4, and Smad 7 increased gradually during the NB4 cells' differentiation induced by ATRA. Their expression reached the peak at 48 h or 72 h and then declined gradually. But there was no significant difference in the dehydrated alcohol-treated group (control). PML-RARα fusion protein and Smad 3 protein were co-localized in NB4 cells. Conclusion: TGF-β1 signaling transduction pathways are closely related with NB4 cells' differentiation. ATRA can up-regulate the mRNA expression levels involved in the signaling transduction pathway. PML-RARα fusion protein is apt to bind with Smad 3 protein.