The Effect of hnRNPK/Beclin1 Signaling on the Drug Resistance of Imatinib in Ph+ Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of hnRNPK/Beclin1 signaling on the drug resistance of imatinib in Ph+ leukemia.@*METHODS@#Expression level of hnRNPK was verified in the imatinib resistant and sensitive Ph+ leukemia cell lines by using Western blot. hnRNPK expression was down-regulated by using RNAi. Expression level of LC3I/II and Beclin1 were detected by Western blot and the sensitivity of imatinib was analyzed by CCK-8 assay before and after modulation of hnRNPK expression.@*RESULTS@#hnRNPK showed overexpressed in imatinib resistant leukemia cell line. After the expression level of hnRNPK was down-regulated by RNAi, the sensitivity of drug resistance lines to imatinib restored, while the expression level of LC3I/II and Beclin1 were consistant with the modulation of hnRNPK expression.@*CONCLUSION@#hnRNP K/Beclin1 signaling may be involved in the development of imatinib resistance in Ph+ leukemia through the regulation of autophagy.

Study on potential molecular mechanism of Mongolian medicine Bawei Sanxiang San in treatment of chronic heart failure based on network pharmacology and molecular docking / 中国中药杂志

To explore the potential molecular mechanism of Mongolian medicine Bawei Sanxiang San in the treatment of chronic heart failure(CHF) through network pharmacology and molecular docking technology. The active ingredients and potential targets of Bawei Sanxiang San were collected by applying TCMSP, BATMAN databases and literature mining. CHF-related genes were collected through TTD, GeneCards and CTD databases. After the potential common targets between Bawei Sanxiang San and CHF were disco-vered, the interaction network diagram of "compound-target-pathway" was constructed using Cytoscape. The intersecting targets were imported into the DAVID database for GO function and KEGG pathway enrichment analysis. Finally, the Autodock_vina software was used to molecularly dock the selected proteins with the active ingredients of Bawei Sanxiang San. The results showed that there were 60 active ingredients in Bawei Sanxiang San that might be used to treat CHF, involving 311 target genes and 7 signaling pathways that directly related to CHF, such as HIF-1 signaling pathway, TNF signaling pathway, adrenergic signaling in cardiomyocytes, aldosterone-regulated sodium reabsorption, calcium signaling pathway, cGMP-PKG signaling pathway, renin secretion. Additionally, molecular docking showed that the bioactive compounds had good binding activity with the protein receptors of key target genes. Bawei Sanxiang San might exert therapeutic effects on CHF by regulating cardiomyocytes, angiogenic and inflammation related targets and pathways in a multi-component, multi-target and multi-pathway manner.

hnRNP K Contributes to Adriamycin Resistance in Acute Myeloid Leukemia through Regulating Autophagy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the role of heterogeneous nuclear ribonucleoprotein(hnRNP) K regulating autophagy in the drug resistance of acute myeloid leukemia, so as to provide a new molecular marker for treatment of leukemia.</p><p><b>METHODS</b>The relationship between the expression level of hnRNP K and the drug resistance of myeloid leukemia was verified by fluorescence quantitative PCR; the expression of autophagy related protein LC3I/ II was detected by Western blot after the hnRNP K was modulated by RNA interference technology; the sensitivity of leukemia cells to doxorubicin was analyzed before and after the expression of hnRNP K were modulatd.</p><p><b>RESULTS</b>The expression of hnRNP K and LC3I/II significantly increased in bone marrow nonremission patients and in drug resistant cell line, however, the expression of LC3I/ II decreased when the expression of hnRNP K were reduced, while the sensitivity of cells to adriamycin could be recovered.</p><p><b>CONCLUSION</b>hnRNP K may be involved in the formation of adriamycin resistance in acute myeloid leukemia by regulating autophagy.</p>

Bioinformatic analysis of chronic myeloid leukemia progression and preliminary experimental verification / 中国实验血液学杂志

This study was aimed to explore the progression mechanism of chronic myeloid leukemia, so as to provide the new molecular markers for evaluation of CML clinical outcome and selection of treatment. The microarray data of genes related with progression from different phase of chronic myeloid leukemia (CML) were collected from public data depository GEO (Gene expression datasets). SAM analysis, fold change filtering, cross comparison were used to analyze the data and identify different genes. Moreover, MeV and pSTIING sofewares were used to analyze the key differential genes and signal pathways. At last, Q-PCR were used to confirm the predicted key gene. The results indicated that after comparison, 9 genes were differentially expressed from AP to BC, and the integrin-mediated cell adhesion , focal adhesion, regulation of actin cytoskeleton were the principal pathways during CML progression. Network construction analysis found that AP-related genes or pathways may be the original signals; and MLLT4, WDR35 and EPHB4 were the key genes for CML progression. EPHB4 was confirmed by Q-PCR in CML BC patients and CP patients. It is concluded that MLLT4, WDR35, EPHB4, integrin-mediated cell adhesion, focal adhesion and regulation of actin cytoskeleton are the principal genes and pathways during CML progression.

Comparison of clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate and compare the clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia (B-ALL).</p><p><b>METHODS</b>A total of 129 cases of de novo childhood (73 cases) and adult (56 cases) B-ALL were examined genetically and immunologically using G-banding techniqhe, interphase fluorescence in situ hybridization (I-FISH) and immunophenotyping by flow cytometry, and their clinical data were retrospectively analyzed.</p><p><b>RESULTS</b>Of 73 childhood cases, the prevalences of homozygous deletion, hemizygous deletion and no deletion of p16 were 24.7% (18 cases), 6.8% (5 cases) and 68.5% (50 cases) respectively, and of 56 adult cases, the incidences as of 14.3% (8 cases), 8.9% (5 cases) and 76.8% (43 cases) respectively. The incidence of p16 deletion between the two groups had no significant difference (P = 0.338). In both groups, patients with or without p16 deletion had no significant difference in terms of white blood cells (WBC) count at diagnosis, BM blast percentage, chromosome karyotype, extra-infiltration and CR1 rate. Of note, there were 2 cases, each in childhood and adult, showed no deletion at the time of diagnosis, their p16 deletions occurred at relapse. The deletion of p16 was associated with poor overall survival and event-free survival (EFS) in both childhood and adults. According to the standard of NCI risk stratification, we divided patients of two groups into standard and high risk category respectively, and performed further analysis. The significance of different risk category in children and adults was disparity. The overall survival (OS) rates of deletion and no deletion of p16 were 45.3% and 79.8% (P = 0.006) in children, and 7.7% and 22.6% (P = 0.002) in adults, respectively. EFS rates of deletion and no deletion of p16 were 33.5% and 58.1% (P = 0.008) in children, and 0 and 10.9% (P < 0.01) in adults, respectively. Of the standard risk category in children, OS rates of deletion and no deletion of p16 were 46.8% and 89.3% (P = 0.015) respectively, and EFS rates of deletion and no deletion of p16 as of 40.9% and 82.1% (P = 0.007) respectively. Of the high risk category in children, OS rates of deletion and no deletion of p16 were 41.7% and 67.4% (P = 0.193) respectively, and EFS rates of deletion and no deletion of p16 were 25.0% and 25.6% (P = 0.305) respectively. Of the standard risk category in adults, OS rates of deletion and no deletion of p16 were 20.0% and 46.9% (P = 0.092) respectively, and EFS rates of deletion and no deletion of p16 were 0 and 25.0% (P = 0.062) respectively. Of the high risk category in adults, OS rates of deletion and no deletion of p16 were 0 and 12.4% (P < 0.001) respectively, and EFS rate of deletion and no deletion of p16 was 0 and 4.8%(P < 0.001), respectively.</p><p><b>CONCLUSION</b>This study indicated that deletion of p16 was associated with poor prognosis in both childhood and adult B-ALL, which highlighted an important significance to define the status of p16 in both childhood and adult B-ALL for predicting prognosis and guiding clinical intervention.</p>

Application of multiprobe fluorescence in situ hybridization panel in the diagnosis of acute myeloid leukemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of multiprobe fluorescence in situ hybridization (FISH) panel in the diagnosis of acute myeloid leukemia (AML).</p><p><b>METHODS</b>The multiprobe AML/MDS panel comprising 8 different FISH probes for AML1/ETO transfusion gene, PML-RARα transfusion gene, CBFβ/MYH11 transfusion gene, MLL breakapart, P53 deletion, Del(5q), -7/Del(7q), and Del(20q) was tested in 40 cases of AML, and the results were compared with those by conventional cytogenetic G-banding (CCG) test.</p><p><b>RESULTS</b>With multiprobe FISH panel, 22 of the 40 AML cases were found to carry 7 types of cytogenetic abnormalities, namely AML1/ETO transfusion gene, PML-RARα transfusion gene, MLL breakapart, P53 deletion, Del(5q), -7/Del(7q) and trisomy 8. The positive ratio of the multiprobe FISH was 57.5%. CCG only identified 8 cases with the corresponding cytogenetic abnormalities and 3 cases with other cytogenetic abnormalities, and the positive ratio was only 27.50%.</p><p><b>CONCLUSION</b>Mutiprobe FISH panel is more rapid, accurate and effective than CCG in the diagnosis of AML.</p>

Fetal cardiac function in fetal cardiac bypass / 中华胸心血管外科杂志

Objective To study the effects of fetal lamb cardiac bypass on the fetal cardiac function.Methods Eight ewes at gestation of 120 to 140 days have nine fetus which were randomly divided into control group (n = 4) and fetal bypass group (n = 5). Control group underwent sham procedure that fetal stemotomy was performed.Bypass group underwent fetal cardiac bypass with cen- trifugal pump and placenta for 30 minutes.Fetal mean blood pressure,heart rate and bleed gas data were recorded before bypass,30 minutes during bypass,1 hour after cessation of bypass,2 hour after cessation of bypass.Tei index of two ventricles and pulse index of umbilical arteries were recorded with ultrasonography.Plasma troponin I was assayed.Ultrastructure of fetal myocardium was recorded,Results Fetal mean blood pressure and heart rate of two groups have no changes during the experiment time.The umbilical pulse index of bypass group elevated significantly compared with control group (P