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ABSTRACT: The fusion gene AML1/ETO is a molecular marker for monitoring minimal residual disease (MRD) in acute myeloid leukemia with the t(8;21)(q22;q22) translocation. To evaluate the dynamic variation and prognostic significance of AML1/ETO, bone marrow samples from 52 patients at different periods were examined qualitatively (32 patients) or quantitatively (20 patients) using nested RT-PCR and RQ-PCR, respectively. In the qualitative group, AML1/ETO in 71.88 and 95.45 % patients became negative at six and 24 months after CR, respectively. Patients in long-term remission were all RT-PCR-negative. Patients negative for AML1/ETO at 6-12 months and 12-18 months after CR had lower relapse rate (P = 0.003 and 0.000), higher relapse-free survival (RFS) (P = 0.000 and 0.000), and overall survival (P = 0.001 and 0.000) than patients with positive AML1/ETO. Quantitative analysis showed that there was no trend where higher relapse rate occurred in patients with higher levels of AML1/ETO transcripts at diagnosis (P > 0.05). Patients whose AML1/ETO transcripts decreased by more than 2 log at CR had higher RFS (P = 0.02). At the checkpoints of 3 and 5/6 months after CR, patients with lower AML1/ETO copy numbers showed lower probability of relapse (P = 0.039 and 0.004). An increase of AML1/ETO transcripts (0.5 log) at any time after CR indicated increased risk of relapse (P = 0.002). Our study shows that both qualitative and quantitative detection of AML1/ETO have prognostic value in MRD monitoring. Negative or continuous low expression of AML1/ETO indicates increased disease-free survival.
International journal of hematology 04/2013; · 1.17 Impact Factor
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Qihui Li,
Lei Huai,
Cuiping Zhang,
Cuicui Wang,
Yujjao Jia,
Yirui Chen,
Pei Yu,
Houcai Wang,
Qing Rao,
Min Wang, Jianxiang Wang
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ABSTRACT: Icaritin, a hydrolytic product of icaritin, is isolated from the traditional Chinese medicinal herb epimedium. Icaritin inhibits the proliferation of several tumor cell lines, but its effect on acute myeloid leukemia (AML) and underlying mechanisms remain to be identified. In the present study, we demonstrated that icaritin inhibits the proliferation of human AML cell lines NB4, HL60, and U937, in a dose- and time-dependent manner. Importantly, icaritin showed anti-leukemia activity on bone marrow mononuclear cells from 15 newly diagnosed AML patients. Flow cytometry analyses indicated that icaritin induces AML cells apoptosis. Icaritin induced activation of caspase-9, -3, -7 and the cleavage of PARP as measured by Western blotting. Icaritin downregulates p-ERK and p-AKT and inhibits the expression of c-myc. These results suggest that icaritin is a promising candidate drug for the treatment of AML. The underlying mechanisms of icaritin anti-AML activity are associated with inhibition of the MAPK/ERK and PI3K/AKT signals and downregulation of c-myc.
International journal of hematology 04/2013; · 1.17 Impact Factor
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ABSTRACT: Mutations at arginine 132 of isocitrate dehydrogenase 1/2 (IDH1/2) have recently been demonstrated to be recurrent gene alterations in acute myeloid leukemia (AML). Subsequently, this mutation was also found in a variety of other hematologic malignancies, including myelodysplastic syndromes, myeloproliferative diseases, and non-Hodgkin lymphoma. Only a few cases were so far identified in acute lymphoblastic leukemia (ALL). To study the IDH status in ALL patients, we analyzed 54 adult and 34 pediatric ALL samples' IDH1/2 gene.
Three adult cases and no pediatric case with an isocitrate dehydrogenase 1 (IDH1) mutation were identified. No isocitrate dehydrogenase 2 (IDH2) mutation was identified in the total of 88 samples. The frequency of the IDH1 mutation in adult ALL was 5.5%. Among the three IDH1-mutated patients, two had normal karyotype and expressed the myeloid lineage markers. All three patients with an IDH1 mutation relapsed or died within 6 months.
The results suggested that the IDH1 R132 mutation might be a recurrent gene alteration in ALL; patients carrying the mutation have a trend to aberrantly express myeloid antigen and the mutation may imply a dismal outcome.
Genetic Testing and Molecular Biomarkers 07/2012; 16(8):991-5. · 1.11 Impact Factor
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ABSTRACT: iASPP was an inhibitory member of ASPP family and could specifically inhibit the apoptotic function of p53. iASPPsv was identified by our lab as the short isoform of iASPP, which encoded a 407 aa protein and highly matched the carboxyl terminus of iASPP. In this study, iASPPsv was stably transfected into the breast cancer cell line MCF-7 by means of lentivirus to explore the effects of iASPPsv on biological functions of MCF-7. Thymocytes from iASPP/iASPPsv transgenic mice were also used to explore the effects of iASPP/iASPPsv on cell biological function. The results demonstrated that iASPPsv antagonized the growth inhibition induced by etoposide (VP-16) in MCF-7 cells. iASPPsv also down-regulated proapoptotic genes (Bax, Puma and Noxa) expression to inhibit apoptosis caused by VP-16. Moreover, iASPP and iASPPsv could both help the thymocytes of transgenic mice to resist the growth inhibition and apoptosis caused by dexamethasone (Dex) or VP-16. At the same time, DNA double strand break damage accumulated in either iASPPsv MCF-7 cells or iASPP/iASPPsv thymocytes. These findings showed that iAPSS/iASPPsv reduced the growth inhibition and apoptosis induced by Dex or VP-16, with DNA damage accumulating which might promote the pathogenesis and/or progression of cancer.
Biochemical and Biophysical Research Communications 07/2012; 424(3):414-20. · 2.48 Impact Factor
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Lei Huai,
Cuicui Wang,
Cuiping Zhang,
Qihui Li,
Yirui Chen,
Yujiao Jia,
Yan Li,
Haiyan Xing,
Zheng Tian,
Qing Rao,
Min Wang, Jianxiang Wang
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ABSTRACT: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RARα and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.
Biochemical and Biophysical Research Communications 05/2012; 422(3):398-404. · 2.48 Impact Factor
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ABSTRACT: Reports on the use of the real-time quantitative polymerase chain reaction (RQ-PCR) for childhood acute promyelocytic leukemia (APL) therapy are scarce. This study describes the prognostic significance of quantification of the PML-RARa transcript in children with APL. Since January 2004, we have analyzed 40 children treated with all-trans-retinoic acid ± arsenic trioxide in induction. Thirty-nine patients (97.5%) entered complete remission. The 5-year rates of disease-free survival (DFS) and overall survival in these patients were 73.1 and 91.4%, respectively. By employing a standardized RQ-PCR protocol for minimal residual disease (MRD) monitoring, we determined that less than 1 normalized copy number (NCN) after induction indicates higher probability of a more favorable treatment outcome. After induction therapy, thirteen out of 38 (34.2%) patients in hematologic remission showed a negative RQ-PCR result (less than 1 NCN), which was correlated with the lower probability of relapse (100 and 55.2% DFS at 5 years in the negative and positive RQ-PCR groups, respectively; P = 0.018). PML/RARa-based MRD monitoring by RQ-PCR may allow us to identify subgroups of patients at low risk of relapse after induction.
International journal of hematology 03/2012; 95(5):500-8. · 1.17 Impact Factor
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Xiaojun Huang,
Fengrong Wang,
Yuhong Chen,
Ting Liu, Jianxiang Wang,
Jianda Hu,
Jin Jie,
Fangping Chen,
Shujie Wang,
Zhixiang Shen,
Li Yu,
Kang Yu,
Yingmin Liang
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ABSTRACT: Invasive fungal infections pose a severe health threat to patients. Despite recent advances in drug development, treatment of recurrent fungal infections remains difficult. Posaconazole is a broad-spectrum triazole antifungal drug available for oral administration. Although initial studies have described its use in treating various fungal infections, its efficacy and safety in patients with invasive fungal infections remains to be further confirmed.
In this study, we performed a multicenter, open-label clinical trial of posaconazole oral suspension in the treatment of 63 patients with invasive fungal infections who were refractory to or intolerant of first-line therapy.
Our result showed that 64.4% of patients had a clinical response after posaconazole treatment, with 52.9% showing eradication of the fungal infection. The treatment caused some adverse effects of mild or moderate severity that were of short duration.
The results of this trial indicate that posaconazole can be used in invasive fungal infections as an alternative or salvage therapy.
Future Microbiology 02/2012; 7(2):201-9. · 3.82 Impact Factor
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Ye Su,
Xin Cheng,
Yaohong Tan,
Yunhui Hu,
Yuan Zhou,
Juanni Liu,
Yuanfu Xu,
Yinliang Xie,
Caiyun Wang,
Yingdai Gao, Jianxiang Wang,
Tao Cheng,
Chunzheng Yang,
Dongsheng Xiong,
Hua Miao
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ABSTRACT: Multidrug resistance mediated by P-glycoprotein in cancer cells has been a major issue that cripples the efficacy of chemotherapy agents. Aimed for improved efficacy against resistant cancer cells, we designed and synthesized 25 oxindole derivatives based on indirubin by structure-activity relationship analysis. The most potent one was named PH II-7, which was effective against 18 cancer cell lines and 5 resistant cell lines in MTT assay. It also significantly inhibited the resistant xenograft tumor growth in mouse model. In cell cycle assay and apoptosis assay conducted with flow cytometry, PH II-7 induced S phase cell cycle arrest and apoptosis even in resistant cells. Consistently revealed by real-time PCR, it modulates the expression of genes related to the cell cycle and apoptosis in these cells, which may contributes to its efficacy against them. By side-chain modification and FITC-labeling of PH II-7, we were able to show with confocal microscopy that not only it was not pumped by P-glycoprotein, it also attenuated the efflux of Adriamycin by P-glycoprotein in MDR tumor cells. Real-time PCR and western blot analysis showed that PH II-7 down-regulated MDR1 gene via protein kinase C alpha (PKCA) pathway, with c-FOS and c-JUN as possible mediators. Taken together, PH II-7 is a dual-functional compound that features both the cytotoxicity against cancer cells and the inhibitory effect on P-gp mediated drug efflux.
PLoS ONE 01/2012; 7(3):e32782. · 4.09 Impact Factor
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ABSTRACT: Knowledge of mixed phenotype acute leukemia (MPAL) with t(9;22)(q34;q11.2) and/or bcr-abl (Ph-positive MPAL) is limited. In this report, we review 21 adult patients with Ph-positive and/or bcr-abl positive MPAL. They were predominantly male, and presented with high WBC counts; 61.9% patients had WBC counts higher than 30 × 10(9)/L, and 33.3% patients had WBC counts higher than 100 × 10(9)/L. Electron microscopy (EM)-determined positivity for myeloperoxidase (MPO) should be considered for the classification of acute leukemia because MPO was positive by EM and flow cytometry only in 14.3% of cases in our study. Six cases (30.0%) had additional chromosome aberrations. Expression of p190(bcr-abl) was more common than that of p210(bcr-abl). There was no difference in characteristics between the p190(bcr-abl) positive and p210(bcr-abl) positive groups. The overall complete remission (CR) rate was 81.0%. Females, and patients with high WBC (>100 × 10(9)/L) at baseline had lower CR rate (57.1, 57.1%, respectively). The treatment outcome of Ph-positive MPAL is poor; the 1-year overall survival (OS) and relapse-free survival (RFS) rate were 28.0 and 18.0%, respectively. Imatinib and allogeneic hematopoietic stem cell transplantation can improve survival with Ph-positive MPAL.
International journal of hematology 12/2011; 94(6):552-5. · 1.17 Impact Factor
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ABSTRACT: A meta-analysis was performed to demonstrate the prognostic significance of FLT3-TKD mutations in acute myeloid leukemia (AML). The overall hazard ratio (HR) of FLT3-TKD/FLT3-wild type (WT) for disease-free survival (DFS) was 1.20. The overall HRs for overall survival (OS) of FLT3-TKD to FLT3-ITD and FLT3-WT were 0.87 and 1.18. For non-promyelocytic AML with intermediate cytogenetics, the overall HR for DFS of FLT3-TKD/FLT3-ITD was 0.71. The HR for OS of FLT3-TKD/FLT3-ITD was 0.75. Adult AML patients with FLT3-TKD mutations exhibit better outcomes than those with FLT3-ITD. The patients with FLT3-TKD mutations with intermediate cytogenetics had similar OS as those with FLT-WT mutations.
Leukemia research 09/2011; 36(2):186-91. · 2.36 Impact Factor
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ABSTRACT: The present study was undertaken to estimate the therapeutic benefit to down-regulate the Na(+)/H(+) exchanger 1 (NHE1) for reversing chemoresistance of BCR-ABL-positive leukemia patient cells and cell lines. As a result, after treatment with specific NHE1 inhibitor Cariporide or high K(+) buffer to decrease intracellular pH (pH(i)), cells from relapsed patients exhibited decreased Pgp level, enhanced Rhodamine123 and drug accumulation, decreased colony-forming ability and the modulations of mitogen-activated protein kinases (MAPKs) activities. Furthermore, we used BCR-ABL-positive cell line K562 and its resistant counterparts K562/DOX and K562/G01 cell lines for further study. Together, these findings suggest that Pgp may be associated with the reversal of drug resistance in BCR-ABL-positive leukemia patients and cell lines by the inhibition of NHE1 though MAPK pathways.
Cancer letters 09/2011; 308(1):81-90. · 4.86 Impact Factor
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ABSTRACT: To investigate the clinical and laboratory characteristics of patients with various hematological malignancies harboring der(1;7)(q10;p10).
Bone marrow samples were collected and undergone short-time unstimulated culture and R-banding, and karyotyped by conventional cytogenetic assay (CCA). Megalokaryocytes were detected by streptavidin-AKP (SAP). Retrospective analyses including the clinical and laboratory data were performed.
Nineteen of the 21 patients were male. Most of the patients are of older age. Thirteen cases (61.9%) were der(1;7)(q10;p10) without additional aberrations, 8(38.1%) patients had additional aberrations. Sixteen out of the 18 cases (88.9%) who underwent SAP analysis had diminutive megalokaryocyte, and lymphoid megalokaryocyte was found in 10 cases (55.6%). The der(1;7) patients manifested poor response to treatment.
The der(1;7) patients demonstrated distinct male predominance, older age at diagnosis, and some clinically distinctive features. These patients showed poor prognosis. The cytogenetic abnormality, i.e., der(1;7)(q10;p10), can be used as a prognostic indicator.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 08/2011; 28(4):441-5.
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ABSTRACT: Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. An aberrant folate metabolism caused by a genetic polymorphism may lead to genomic instability and affect the susceptibility to malignancies including acute lymphoblastic leukemia (ALL). This study was designed to explore the correlation between the polymorphisms in folate-related genes and the risk of ALL in Han Chinese. The DNA was isolated from 231 patients with pediatric ALL, 130 patients with adult ALL, and 367 healthy subjects (as controls). Polymorphisms were examined for RFC1 80G > A, DHFR 19 bp del/ins and 317A > G, SHMT1 1420C > T, MTHFR 677C > T and 1298A > C, MTR 2756A > G, MTRR 66A > G, TYMS 3R/2R, MTHFD1 1958G > A, and ABCG2 421G > T using real-time polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP). The risk of adult ALL was increased by the RFC1 80AA variant (odds ratio [OR] = 2.09; 95% confidence interval [CI] 1.19-3.67) and MTRR 66GG variant (OR = 2.15; 95% CI 1.06-4.39) but reduced by the MTHFR 677TT variant (OR = 0.47; 95% CI 0.25-0.88), ABCG2 421GT variant (OR = 0.62; 95% CI 0.41-0.96), and ABCG2 421GT + TT variant (OR = 0.60; 95% CI 0.40-0.90). The increase in risk of adult ALL with the RFC1 80AA associated with the MTRR 66GG variant was even more significant (OR = 8.92; 95% CI 1.97-40.42). Furthermore, the MTHFR 677TT associated with the ABCG2 421GT + TT variant more significantly reduced the risk of adult ALL (OR = 0.32; 95% CI 0.12-0.85). However, all gene polymorphisms tested in this study failed to affect the pediatric ALL risk. Our study clearly demonstrates that polymorphisms in folate-related genes only modulate the susceptibility to adult ALL, but not to pediatric ALL, in Han Chinese.
Leukemia & lymphoma 06/2011; 52(9):1770-6. · 2.40 Impact Factor
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ABSTRACT: KIT mutations may be associated with a poor prognosis in t(8;21) AML. Heat shock protein 90 (Hsp90) is a molecular chaperone frequently used by cancer cells to stabilize mutant oncoproteins. Inhibition of Hsp90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) disrupted downstream signaling pathways of mutant KIT in Kasumi-1 cells. AML1-ETO fusion gene and mutated KIT act as "two-hit" factors in Kasumi-1 cells. Histone deacetylation (HDAC) inhibitors sodium phenylbutyrate (PB) and valproic acid (VPA) block AML1-ETO. Co-treatment with 17-AAG and PB or 17-AAG and VPA resulted in a synergistic effect in Kasumi-1 cells. Our results confirmed that Hsp90 and mutated KIT were valid molecular targets in the therapy of AML.
Leukemia research 05/2011; 35(9):1212-8. · 2.36 Impact Factor
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ABSTRACT: DNA double-strand break repair via homologous recombination (HR) is essential in maintaining genetic integrity, and may modulate susceptibility to the development of acute myeloid leukemia (AML) and influence outcomes of AML. This study was designed to evaluate the effects of polymorphisms in HR repair genes RAD51 and XRCC3 on the risk and treatment outcomes of inv(16)/t(16;16)/CBFβ-MYH11(+) AML. The distribution of polymorphisms in RAD51-G135C and XRCC3-Thr241Met were studied by PCR-RFLP analysis in 625 cases of de novo AML, including 105 cases with inv(16)/t(16;16)/CBFβ-MYH11, 806 family controls and 704 volunteer controls. It was found that the XRCC3-241Met variant significantly increased the risk of the development of the AML with inv(16)/t(16;16) as compared with both the volunteer control (OR=7.22; 95% CI, 4.37-11.91) and the family control (OR=7.99; 95% CI, 5.03-12.69). A retrospective study conducted in 103 inv(16)/t(16;16) AML patients. In multivariate analysis for the potential prognostic factors, the XRCC3-241Met variant significantly reduced disease-free survival (DFS) in complete remission (CR) achieved patients (HR=2.34, 95% CI, 1.32-4.16). These data indicate that the XRCC3-241Met variant may not be only a susceptibility factor to the AML with inv(16)/t(16;16), but also an independent poor-prognostic factor for this AML subtype.
Leukemia research 02/2011; 35(8):1020-6. · 2.36 Impact Factor
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Yiqun Zhang,
Hui Wei,
Min Wang,
Lei Huai,
Yingchang Mi,
Yizhi Zhang,
Dong Lin,
Bingcheng Liu,
Wei Li,
Chunlin Zhou,
Qing Rao, Jianxiang Wang
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ABSTRACT: Mutations of isocitrate dehydrogenase 1 (IDH1) have recently been reported in acute myeloid leukemia (AML). However, the characteristics of IDH1-mutated AML are still not known clearly. We analyzed 416 Chinese AML patients and found 28 patients (6.7%) carried this mutation. One homozygous IDH1 mutant in AML was found. The IDH1 mutations were associated with NPM1 mutations (P=0.043) and could coexist with recurrent transcription factor aberrations including AML1-ETO (6/50), PML-RARα (3/77) and CBFβ-MYH11 (1/15). For AML with AML1-ETO fusion gene, IDH1(mut) patients may have worse disease-free survival (DFS) than IDH1(wild-type) patients.
Leukemia research 02/2011; 35(10):1301-6. · 2.36 Impact Factor
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Lei Zhi,
Jianwei Zhang,
Yujiao Jia,
Shilong Shan,
Yan Li,
Donghai Wang,
Min Wang,
Qing Rao,
Haiyan Xing,
Kejing Tang,
Zheng Tian, Jianxiang Wang,
Yingchang Mi
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ABSTRACT: G-rich oligonucleotides (GROs) can inhibit cell proliferation by inducing cell cycle arrest at S phase in tumor cell lines. GROs bind specific cellular proteins, such as nucleolin, a crucial protein interacting with P53; however, little is known about the relationship between GROs and P53. In this study, we have shown that GROs inhibited the proliferation of U937 cells (a human monocytic leukemia cell line without P53 expression) by inducing S-phase arrest. We also showed that GRO colocalized with nucleolin in U937 cells. GRO treatment induced alteration of a series of cell cycle regulatory proteins in U937 cells. Increased Cdk2 expression might promote the cells to enter S phase and subsequent decrease of Cdk2 might induce cell cycle arrest in S phase. Transfection of U937 cells with a wild-type p53 gene caused the formation of nucleolin-P53 complex, which alleviated the effect of GRO on leukemia cells. This alleviated effect is probably due to the decreased uptake of GRO.
Oligonucleotides 02/2011; 21(1):21-7. · 2.80 Impact Factor
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ABSTRACT: To assess the incidence rates and risk factors for clonal evolutions in aplastic anemia (AA) patients, we studied 802 hospitalization cases from January 1991 through December 2007 by using the cumulative incidence curves and the Cox proportional hazards mode. We found that the case of 19 patients had evolved to myelodysplastic syndrome or acute myeloid leukemia (MDS/AML), while 21 patients (two of them with concurrent MDS) developed paroxysmal nocturnal hemoglobinuria (PNH). The cumulative incidence of clonal evolutions was assessed as 3.7%, whereas the incidences of MDS/AML and PNH were 1.7% and 2.1%, respectively, at 5 years. By multivariate analysis, age, severity of the disease, and the number of days of rhuG-CSF therapy were the risk factors for AA evolution to MDS/AML. The relative risk (RR) for very severe AA was approximately seven times higher than that for severe AA (SAA) and non-SAA (NSAA) (P = 0.001), but the latter two did not differ significantly (P = 0.743). PNH clone was monitored sequentially in 237 patients; positive clones were detected in 41% of the patients, but more than half of them were transient or instable. White blood cell count at initial diagnosis was identified as the only significant risk factor for AA evolution to PNH (P = 0.007). Our results suggest that the transformation to PNH for subpopulations of AA patients may be natural evolution as the clinical manifestation and pathogenesis between AA and PNH were closely related. Furthermore, normalizing hematopoiesis of AA may represent a viable approach to prevent clone evolutions, especially to MDS/AML.
Annals of Hematology 01/2011; 90(5):529-37. · 2.62 Impact Factor
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ABSTRACT: E-cadherin (epithelial cadherin) belongs to the calcium-dependent adhesion molecule superfamily and is implicated in the interactions of haematopoietic progenitors and bone marrow stromal cells. Adhesion capacity to bone marrow stroma was impaired for leukaemia cells, suggesting that a breakdown of adhesive mechanisms governed by an adhesion molecule may exist in leukaemic microenvironment. We previously found that E-cadherin was low expressed in primary acute leukaemia cells compared with normal bone marrow mononuclear cells. In this study, we investigate the functional importance of low E-cadherin expression in leukaemia cell behaviours and investigate its effects in the abnormal interaction of leukaemic cells with stromal cells. After expression of E-cadherin was restored by a demethylating agent in leukaemia cells, E-cadherin-specific adhesion was enhanced. Additionally, siRNA (small interfering RNA)-mediated silencing of E-cadherin in Raji cells resulted in a reduction of cell homophilic adhesion and enhancement of cell proliferation and colony formation. These results suggest that low expression of E-cadherin contributes to the vigorous growth and transforming ability of leukaemic cells.
Cell Biology International 12/2010; 35(9):945-51. · 1.48 Impact Factor
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American Journal of Hematology 05/2010; 85(5):378-9. · 4.67 Impact Factor
