miR-4792 Inhibits Acute Myeloid Leukemia Cell Proliferation and Invasion and Promotes Cell Apoptosis by Targeting Kindlin-3

It has been reported that kindlin-3 expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and precise mechanisms of kindlin-3 in acute myeloid leukemia (AML) have not been well clarified. Our study aimed to explore the interaction between kindlin-3 and miR-4792 in AML. In our study, we found that the expression of kindlin-3 was dramatically increased in AML samples and cell lines, and the miR-4792 level was significantly downregulated. Interestingly, the low miR-4792 level was closely associated with upregulated kindlin-3 expression in AML samples. Moreover, introduction of miR-4792 dramatically suppressed proliferation and invasion and induced apoptosis of AML cells. We demonstrated that miR-4792 could directly target kindlin-3 by using both bioinformatics analysis and luciferase reporter assay. In addition, kindlin-3 silencing had similar effects with miR-4792 overexpression on AML cells. Overexpression of kindlin-3 in AML cells partially reversed the inhibitory effects of miR-4792 mimic. miR-4792 inhibited cell proliferation and invasion and induced apoptosis of AML cells by directly downregulating kindlin-3 expression, and miR-4792 targeting kindlin-3 was responsible for the regulation of the proliferation, invasion, and apoptosis of AML cells.     

MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA- 204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeatcontaining 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3 -UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.     

How to Establish Acute Myeloid Leukemia Xenograft Models Using Immunodeficient Mice

The discovery of the immunodeficient mice has provided a tool for establishing animal models as hosts for invivo analysis of AML. Various model systems have been established in the last few decades, and it is essential thatmurine AML models are developed to exploit more specific, targeted therapeutics. In this review, we concentrate onthe models of AML and discuss the development of immunodeficiency models for understanding of leukemogenesis,describe those now available and their values and document the methods used for establishing and identifyingAML mice models, as well as factors influencing engraftment of human AML in immunodeficient mice. Thus,the function of this article is to provide clinicians and experimentalists with a chronological, comprehensiveappraisal of all AML model systems.     

急性髓系白血病患者HOX11基因的表达及意义

目的 探讨HOX11基因在急性髓系白血病(acute myeloid leukemia,AML)中的表达及对预后的影响,为个体化治疗提供依据.方法 应用多重巢式RT-PCR方法对73例初诊AML患者的融合基因进行检测,对HOX11基因表达阳性和阴性的患者进行标准治疗后的疗效进行分析.结果 在预后良好组、预后中等组及预后不良组AML患者的标准治疗中,HOX11基因阳性表达患者的第一疗程完全缓解率(complete remission rate)并不高于阴性表达的患者(P＞0.05),而复发或死亡率(relapse or mortality rate)与HOX11基因阴性表达的患者比较差异有统计学意义(P＜0.05).结论 HOX11基因的表达可能影响AML患者的预后.     

The Binding of Acute Myeloid Leukemia Blast Cells to Human Endothelium

AML blast cell adhesion to endothelium is in all likelihood a prerequisite for blast cell migration across the vascular wall in the periphery and the subsequent establishment of leukemic extravascular disease. A general feature of malignant cells is their acquisition of altered or aberrant adhesive capabilities which appear to be associated with their ability to metastasize. Aberrant expression of integrin adhesion molecules and of membrane oligosaccharide structures is found in AML and various solid tumors. With respect to AML, these alterations in adhesive phenotype may confer a proliferative advantage on the malignant cells in the marrow, may facilitate egress from the bone marrow into the peripheral vasculature and may enable AML blast cells to traverse the vessel wall and so establish extravascular disease. Oncogenes may be directly involved in the acquisition of such aberrant adhesive phenotypes. Neutrophil extravasation is described as a model for leukocyte migration across the vessel wall and brief summaries of experimental work involving aspects of AML blast cell and normal CD34+ bone marrow cell adhesion to endothelium in vitro are described.     

Monosomal Karyotypes among 1147 Chinese Patients with Acute Myeloid Leukemia: Prevalence,Features and Prognostic Impact

A monosomal karyotype (MK), defined as ≥2 autosomal monosomies or a single monosomy in the presenceof additional structural abnormalities, was recently identified as an independent prognostic factor conveying anextremely poor prognosis in patients with acute myeloid leukemia (AML). In the present study, after excludingpatients with t(15;17), t(8;21), inv(16) and normal karyotypes, 324 AML patients with cytogenetic abnormalitieswere the main subject of analysis. The incidences of MK were 13% in patients aged 15 to 60 years and 18% inthose between 15 and 88 years old. MK was much more prevalent among elderly patients (p < 0.001) and wassignificantly associated with the presence of -7, -5, del(5q), abn12p, abn17p, -18 or 18q-, -20 or 20q- and CK (forall p < 0.001 except for abn12p p=0.009), and +8 or +8q was less frequent in MK+ AML(p=0.007). No correlationwas noted between monosomal karyotype and FAB subtype (p > 0.05); MK remained significantly associatedwith worse overall survival among patients with complex karyotype (p= 0.032); A single autosomal monosomycontributed an additional negative effect in OS of patients with structural cytogenetic abnormalities (P=0.008).This report presents the prevalence, feature and prognostic impact of MK among a large series of Chinese AMLpatients from a single center for the first time.     

HIA与IA方案治疗初治急性髓系白血病的临床对比观察

目的分别用去甲氧柔红霉素（IDA）与HA方案[高三尖杉酯碱（HH）+阿糖胞苷（Ara-C）]组成的双诱导HIA方案与传统IA方案治疗初治急性髓系白血病,比较两组化疗方案的疗效及不良反应。方法HIA方案为：IDA 7 mg/（m²·d）,静脉滴注第1~3天;HH 2.5 mg/（m²·d）,静脉滴注,第1~5天;Ara-C 100 mg/（m²·d）,静脉滴注,第1~5天。IA方案为：IDA 10 mg/（m²·d）,静脉滴注,第1~3天; Ara-C 100 mg/（m²·d）,静脉滴注,第1~5天。结果HIA方案组第一疗程 74.4%（32/43）获CR,其中9例复发（早期复发1例,晚期复发8例）。IA方案组第一疗程73.3%(26/30）达CR,其中8例复发（早期复发5例,晚期复发3例）。两组在CR率和生存分析比较上差异均无明显统计学意义。但HIA方案组患者心脏不良反应发生率（2.3%）显著低于IA组（16.7%）。HIA方案化疗的不良反应主要为骨髓抑制和粒细胞缺乏所致感染,未见严重的非造血系统不良反应,尤其未加重心脏毒性,治疗过程中未发生早期死亡。结论HIA方案可以减少蒽环类药物的剂量,不加重心脏毒性,增加了患者的耐受能力,且不影响疗效。     

A Combined Chemical,Computational, and In Vitro Approach Identifies SBL-105 as Novel DHODH Inhibitor in Acute Myeloid Leukemia Cells

Inhibition of the dihydroorotate dehydrogenase (DHODH) has been successful at the preclinical level in controlling myeloid leukemia. However, poor clinical trials warrant the search for new potent DHODH inhibitors. Herein we present a novel DHODH inhibitor SBL-105 effective against myeloid leukemia. Chemical characteristics were identified by ¹H NMR, ¹³C NMR, and mass spectroscopy. Virtual docking and molecular dynamic simulation analysis were performed using the automated protocol with AutoDock-VINA, GROMACS program. Human-recombinant (rh) DHODH was used for enzyme inhibition study. THP-1, TF-1, HL-60, and SKM-1 cell lines were used. MTT assay was used to assess cell viability. Flow cytometry was employed for cell cycle, apoptosis, and differentiation analysis. Chemical analysis identified the compound to be 3-benzylidene-6,7-benz-chroman-4-one (SBL-105). The compound showed high binding efficacy toward DHODH with a DG_bindingscore of −10.9 kcal/mol. Trajectory analysis indicated conserved interactions of SBL-105–DHODH to be stable throughout the 200-ns simulation. SBL-105 inhibited rh DHODH with an IC₅₀ value of 48.48 nM. The GI₅₀values of SBL-105 in controlling THP-1, TF-1, HL-60, and SKM-1 cell proliferations were 60.66, 45.33, 73.98, and 86.01 nM, respectively. A dose-dependent increase in S-phase cell cycle arrest and total apoptosis was observed by SBL-105 treatment in both cell types, which were reversed in the presence of uridine. The compound also increased the differentiation marker CD11b-positive populations in both THP-1 and TF-1 cells, which were decreased under uridine influence. SBL-105, a novel DHODH inhibitor, identified using computational and in vitro analysis, was effective in controlling AML cells and needs attention for further preclinical developments.     

Differential Implications of CSF3R Mutations in t(8;21) and CEBPA Double Mutated Acute Myeloid Leukemia

BackgroundFew data are available exploring mutations of the colony-stimulating factor 3 receptor (CSF3R) in acute myeloid leukemia (AML) in an all-round and systematic manner. The purpose of this study was to analyze the CSF3R mutations (CSF3R_mut) in AML with recurrent genetic abnormalities for potential synergistic pathomechanism.Patients and MethodsWe retrospectively screened 1102 adult de novo AML patients with available next-generation sequencing (NGS) information on 132 genes related to hematologic disorders. The χ², Mann-Whitney U tests were used to analyze their associations with clinicopathologic characteristics, and a propensity score matching (PSM) followed by Kaplan-Meier method was applied to measure their prognostic effects.ResultsOverall, CSF3R_mut were detected in 40 (3.6%) of 1102 patients with adult de novo AML. CSF3R_mut were predominantly enriched in AML with the CEBPA double mutations (CEBPA_dm) (16/122, 13.1%), t(8;21) (12/186, 6.5%) and mutated RUNX1 (3/50, 6.0%), respectively. The CSF3R_mut loci and types differed according to AML subtypes, with frameshift-indels and premature stop confined in the t(8;21) AML [10/12 (83.3%)], and missense recurrently aggregated in the CEBPA_dm AML [16/16 (100%)]. Cases with CSF3R_mut had a lower WBC count versus those with CSF3R wild-type (CSF3R_wt) in the t(8;21) AML cohort, with a borderline significance [median 5.45 (range 0.94-20.30) × 10⁹/L) vs. 8.80 (range 0.96-155.00) × 10⁹/L, P = .046]. CSF3R_mut were non-significantly associated with higher WBC counts [median 33.6 (range 6.8-287.6) × 10⁹/L vs. 18.1 (range 1.7-196.0) × 10⁹/L, P = .156] and significantly with lower immunophenotypic CD15 positivity [0/8 (0%) vs. 44/80 (55%), P = .009] as compared to CSF3R_wt in the CEBPA_dm AML cohort. After propensity score matching followed by Kaplan-Meier analysis, CSF3R_mut cases had comparable disease-free survival (DFS) and overall survival (OS) to those with CSF3R_wt (P = .607 and P = .842, respectively) in the t(8;21) AML cohort. By contrast, CSF3R_mut showed an inclination towards inferior DFS compared to CSF3R_wt in the CEBPA_dm AML cohort [median DFS 19.8 (95%CI 3.1-36.5) months vs. not reached (NR), P = .086]. No significant difference was found for OS between CSF3R_mut and CSF3R_wt cases (P = .943).ConclusionWe concluded that CSF3R_mut were frequently enriched in patients with t(8;21) and CEBPA_dm subtypes among AML, but showed divergent clinicopathologic features, mutation loci and types and differing prognostic aspects.     

NET1 Enhances Proliferation and Chemoresistance in Acute Lymphoblastic Leukemia Cells

Acute lymphoblastic leukemia (ALL) is the most prevalent of pediatric cancers. Neuroepithelial cell-transforming 1 (NET1) has been associated with malignancy in a number of cancers, but the role of NET1 in ALL development is unclear. In the present study, we investigated the effect of NET1 gene in ALL cell proliferation and chemoresistance. We analyzed GEO microarray data comparing bone marrow expression profiles of pediatric B-cell ALL samples and those of age-matched controls. MTT and colony formation assays were performed to analyze cell proliferation. ELISA assays, Western blot analyses, and TUNEL staining were used to detect chemoresistance. We confirmed that NET1 was targeted by miR-206 using Western blot and luciferase reporter assays. We identified NET1 gene as one of the most significantly elevated genes in pediatric B-ALL. MTT and colony formation assays demonstrated that NET1 overexpression increases B-ALL cell proliferation in Nalm-6 cells. ELISA assays, Western blot analyses, and TUNEL staining showed that NET1 contributes to ALL cell doxorubicin resistance, whereas NET1 inhibition reduces resistance. Using the TargetScan database, we found that several microRNAs (miRNAs) were predicted to target NET1, including microRNA-206 (miR- 206), which has been shown to regulate cancer development. To determine whether miR-206 targets NET1 in vitro, we transfected Nalm-6 cells with miR-206 or its inhibitor miR-206-in. Western blot assays showed that miR-206 inhibits NET1 expression and miR-206-in increases NET1 expression. Luciferase assays using wild-type or mutant 3 -untranslated region (3 -UTR) of NET1 confirmed these findings. We ultimately found that miR-206 inhibits B-ALL cell proliferation and chemoresistance induced by NET1. Taken together, our results provide the first evidence that NET1 enhances proliferation and chemoresistance in B-ALL cells and that miR-206 regulates these effects by targeting NET1. This study therefore not only contributes to a greater understanding of the molecular mechanisms underlying B-ALL progression but also opens the possibility for developing curative interventions.     

索拉非尼靶向治疗FLT3-ITD阳性急性髓系白血病

FMS样酪氨酸激酶-3（FLT3）近膜区的的内部串联重复序列（FLT3 internal tandem duplications, FLT3/ITD）突变是急性髓系白血病中常见的基因突变类型,与急性髓系白血病（acute myeloid leukemia, AML）的发生发展及不良预后有密切关系。目前多靶点酪氨酸激酶抑制剂药物的研究成为近几年来治疗FLT3/ITD阳性AML研究的热点,尤其是对多靶点抑制剂索拉非尼（sorafenib）的研究较为深入。本文通过学习国内外相关文献资料,综述酪氨酸激酶抑制剂索拉非尼在治疗FLT3/ITD 阳性AML的疗效和作用机制方面的研究进展。     

Two Novel Mutations of the NPM1 Gene in Syrian Adult Patients with Acute Myeloid Leukemia and Normal Karyotype

Objective: Somatic mutations in exon 12 of the NPM1 gene is one of the most common genetic abnormalities in adult acute myeloid leukemia (AML), which is observed in 25-35% of AML patients and in 50-60% of patients with cytogenetically normal AML (CN-AML). Methods: We performed Sanger sequencing of exon 12 of the NPM1 gene, on 44 CN-AML patients to characterize NPM1 status. Results: In this study, NPM1 mutations were identified in 10 (22.7%) of the 44 CN-AML patients. Among the 10 patients with NPM1 mutations, type A NPM1 mutations were identified in 8 (80%) patients, whereas non-A type NPM1 mutations were observed in 2 (20%) patients. Two non-A type NPM1 mutations were not previously reported: c.867-868InsCGGA and c.861-862InsTGCA. These two novel mutant proteins display a nuclear export signal (NES) motif (L-xxx-L-xx-V-x-L) less frequently and L-x-Lx-V-xx-V-x-L it has been never seen before, yet. However, both novel mutations show a tryptophan loss at codon 288 and 290 at the mutant C-terminus which are crucial for aberrant nuclear export of NPM into the cytoplasm. Conclusions: This study suggests previously unreported NPM1 mutations may be non-rare and thus additional sequence analysis is needed along with conventional targeted mutational analysis to detect non type-A NPM1 mutations.     

Prognostic Relevance of DNMT3A,FLT3 and NPM1 Mutations in Syrian Acute Myeloid Leukemia Patients

Objective: Among all types of hematological neoplasms, acute myeloid leukemia (AML) has the highest death rate. Recently, cytogenetic and molecular genetics are crucial in the management, as a consequence of their effect on AML pathogenesis, classification, risk-stratification, prognosis and treatment. Methods: 100 Syrian adults with Normal Karyotype (NK) newly diagnosed  AML patients were included in this study, all cases confirmed histologically and immunohistochemically. Patients were divided into six subgroups using flow cytometry and cytological results. Polymerase chain reaction (PCR) was performed on exon 11-12 for FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), exon 12 for Nucleophosmin1 (NPM1), and exon 23 for DNA methyltransferase 3A (DNMT3A) using target primers, the electropherograms were analyzed for gene mutations by comparing with the reference DNA sequence. Data were compared and aligned with different sequences using the NCBI BLAST Assembled Genomes tool. Results: FLT3-ITD, NPM1 and DNMT3A were detected in 24%, 22 % and 4%  patients respectively. M2 subtype had the most frequent incidence of diagnosis in AML. FLT3-ITD mutation patients had the highest mean of death cases, while the DNMT3A mutation patients had the lowest. On the other hand, the highest mean of remission was in patients with NPM1 mutation and the lowest in the carriers of the FLT3-ITD mutation. It was observed that the mean relapsed patients with FLT3-ITD and DNMT3A mutation was 3.4 and 2 months respectively, with no significant differences between (FLT3-ITD and DNMT3A) carriers and non-carriers relapsed. On the contrary,  the mean relapsed for NPM1 mutation carriers was 2.4  months with significant statistical differences. The mean survival time for patients with FLT3-ITD and NPM1  mutation was 5.9 months and 5.85 months respectively, with significant correlation. Between it was 5.88 months in DNMT3A patients with no significant differences. Finally, It was noted that the mean event free survival (EFS) of FLT3-ITD mutation patients was 4.818 months and the mean EFS of NPM1 mutation patients was 4.805 months, with significant statistical differences (p<0.05) between the mutation patients and non-mutated patients regarding to EFS, While this mean was not statistically significant in patients carrying DNMT3A mutation. Conclusion: Patients with FLT3-ITD and NPM1 mutations have the worst prognosis, where the presence of those mutations was significantly related to overall survival (OS) and EFS. Our study reflects that DNMT3A was not an extremely bad prognostic effect as an independent factor. We can declare according to this study that genetic mutation and variants detection could easily be incorporated into the regimen evaluation of AML patients.     

IL-2和IL-10在急性髓性白血病患儿血清中的水平及其临床意义

目的 观察急性髓性白血病患儿血清中白细胞介素(IL)-2和IL-10的水平及其临床意义.方法 纳入急性髓性白血病患儿80例,其中初发27例、缓解25例、复发28例.同期纳入体检健康者50例患儿为对照组.应用酶联免疫吸附法(Elisa)检测血清中IL-2和IL-10水平.结果 与对照组比较,急性髓性白血病患儿血清中IL-2水平显著降低,IL-10水平显著升高(P<0.01).血清中IL-2和IL-10水平与急性髓性白血病患儿的年龄、性别、骨髓中白血病细胞比例、FAB分型无显著相关性(P>0.05).急性髓性白血病初发和复发组患儿血清中IL-2和IL-10水平与缓解组比较,有统计学差异(P<0.01).急性髓性白血病初发与复发患儿血清中IL-2和IL-10水平比较,无统计学意义(P>0.05).结论 急性髓性白血病患儿血清中IL-2和IL-10水平变化明显,与该病的预后联系密切.     

BCR/ABL mRNA Targeting Small Interfering RNA Effects on Proliferation and Apoptosis in Chronic Myeloid Leukemia

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment.Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusionprotein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the fivecandidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations (IC50) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes ofapoptosis such as shrunken, fragmentation nucleus as well as “apoptotic bodies” after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.     

急性髓系白血病患者造血微环境中EPCs数量、微血管密度与VEGFR-2表达的意义北大核心CSCD

目的探讨急性髓系白血病(AML)患者外周血及骨髓中内皮祖细胞(EPCs)的数量变化以及骨髓活检标本中微血管密度(MVD)和血管内皮生长因子受体-2(VEGFR-2)表达的临床意义。方法采用流式细胞仪检测30例AML患者以及10例健康对照组外周血及骨髓中EPCs的数量,进行相对及绝对计数;应用常规石蜡包埋骨髓病理切片进行免疫组织化学染色检测30例AML患者骨髓活组织中MVD和VEGFR-2表达水平,分析其与临床特征的关系。结果 (1)治疗前AML患者外周血和骨髓中EPCs计数与对照组比较,差异有统计学意义(P<0.01);治疗后AML患者完全缓解(CR)组与未缓解(NR)组外周血中EPCs比较,差异有统计学意义(P<0.01);CR与NR组骨髓中EPCs计数比较差异也有统计学意义(P<0.05)。(2)AML骨髓切片上MVD和VEGFR-2表达水平与健康对照组比较差异有统计学意义(P<0.05)。经Spearman秩相关检验,EPCs绝对计数、MVD、VEGFR-2三者之间呈正相关关系。(3)观察外周血中EPCs绝对计数≥20个/微升以及<20个/微升两组生存曲线,以100周为观察终点,<20个/微升组生存期明显优于前者。(4)经Cox回归分析,发现治疗前外周血EPCs绝对计数、WBC计数、VEGFR-2、β2-微球蛋白为危险因素。骨髓巨核细胞数与ECOG评分为保护因素。结论 EPCs计数结合MVD和VEGFR-2检测对评价AML血管内皮功能可能有一定的临床意义,可作为判断患者疗效及预后的指标之一。     

COX-2在急性髓细胞白血病中的表达和临床意义的初步研究

目的 探讨环氧化酶2（COX-2）基因在急性髓细胞白血病（AML）中的表达和意义及其对预后的影响。方法 采用Real time PCR检测AML患者中COX-2 mRNA的表达水平,分析COX-2表达水平与AML临床病理特征和预后的关系。采用Kaplan-Meier 法分析COX-2表达与总生存期（OS）的关系。结果 38例AML患者COX-2 mRNA相对表达量的均值为4.77±2.21,其中20例患者为COX 2高表达（8.33±1.96）,18例患者为低表达（1.89±1.04）。COX-2表达与初诊白细胞计数和初次治疗反应有关,与性别和年龄无关。COX-2高表达者的中位OS为16.2个月,低于低表达者的25.6个月（P=0.041）。结论 COX-2表达水平与AML患者的生存有关,其高表达可能是AML的不良预后因素。     

Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/b-Catenin Signaling Pathway

Profilin 2 (PFN2) was found to be mainly expressed in neurons and involved in the development of the brain. In recent years, emerging evidence indicated that PFN2 is also significantly upregulated in various cancers including head and neck cancer (HNSC) and influences cancer cell proliferation, migration, and invasion. However, the role of PFN2 in HNSC development and progression remains unclear. The aim of our study was to investigate the role of PFN2 in the development of HNSC and its possible molecular mechanisms. Bioinformatics showed that increased expression of PFN2 in tumors correlated highly with poor prognosis of HNSC patients. Our results indicated that PFN2 was highly expressed in HNSC tissues and in HNSC cell lines. Knockdown of PFN2 inhibited proliferation, invasion, and migration of HNSC cells, while PFN2 overexpression produced the opposite effects. Using a nude mouse xenograft model, we substantiated the tumor-promoting effect of PFN2 on HNSC in vivo. Furthermore, we found that PFN2 downregulation reduced the phosphorylation of Akt and GSK-3 and reduced the expression of -catenin in HNSC cells. The opposite was observed when PFN2 was overexpressed. Collectively, these results suggest that PFN2 promotes the proliferation and metastasis of HNSC by activating the PI3K/Akt/ -catenin signaling pathway. Although further validation is needed, we speculate that PFN2 plays a crucial role in HNSC and may be a promising therapeutic target and prognostic biomarker.