G-CSFR IV型异构体在成年急性髓系白血病的表达及其临床意义

本研究旨在探讨G-CSFR IV型异构体在成年急性白血病患者中的表达及其临床意义。以19例正常骨髓造血干细胞为对照,利用定量RT-PCR检测正常对照、99例成年AML和34例ALL患者的G-CSFR IV/G-CSFR I型异构体的相对表达水平,并对其中84例AML(非M3)患者的临床特征及化疗效果进行分析。结果表明,GCSFR IV/G-CSFR I相对表达水平在AML患者较ALL患者及正常造血干细胞组高,而G-CSFR IV/G-CSFR I的相对表达水平在ALL患者组与正常造血干细胞组差别无统计学意义。AML(非M3)患者的临床特征及疗效分析显示,G-CSFR IV/G-CSFR I相对高表达的患者比低表达的患者的临床CR率低。G-CSFR IV/G-CSFR I相对表达水平与AML(非M3)患者的性别、年龄、幼稚细胞比例、FAB分型、染色体和融合基因所作的危险分层之间无相关性。结论:G-CSFR IV异构体异常高表达与急性髓系白血病预后差相关。

Acute liver failure due to natural killer-like T-cell leukemia/ lymphoma: A case report and review of the Literature

Acute liver failure （ALF） is a medical emergency requiring immediate evaluation for liver transplantation. We describe an unusual case of a patient who presented with ascites, jaundice, and encephalopathy and was found to have ALF due to natural killer （NK）-Iike T cell leukemia/lymphoma. The key immunophenotype was CD2＋, CD3＋, CD7＋, CD56＋. This diagnosis, which was based on findings in the peripheral blood and ascitic fluid, was confirmed with liver biopsy, and was a contraindication to liver transplantation. A review of the literature shows that hematologic malignancies are an uncommon cause of fulminant hepatic failure, and that NK-like T-cell leukemia/lymphoma is a relatively recently recognized entity which is characteristically CD3＋ and CD56＋. This case demonstrates that liver biopsy is essential in diagnosing unusual causes of acute liver failure, and that infiltration of the liver with NK-like T-cell lymphoma/leukemia can cause acute liver failure.

CLINICAL SIGNIFICANCE OF THE DETECTION OF MINIMAL RESIDUAL DISEASE IN CHILDHOOD B-ALL BY FLOW CYTOMETRY

Objective To detect the minimal residual disease in children with B-ALL and to evaluate its clinical significance by flow cytometry. Methods 58 childhood B-ALL cases were enrolled into this study and 33 MRD analyses were performed after remission induction therapy.Four-color combinations of fluorochrome labeled monoclonal antibodies against lymphocyte lineage related phenotypes were used to analyze leukemic cells with flow cytometry.The cells from normal bone marrow were used as controls.The combinations of phenotypes that reflect the antigen expression differences between leukemic and normal bone marrow cells on flow cytometry were considered to be the effective phenotype combinations in the first step screening.The effective phenotype combinations were then used to monitor MRD during the disease course after therapy began. Results 58 cases of childhood B-ALL were screened for MRD effective phenotype combinations.The effective phenotype combinations were identified in 89.7% of B-ALL cases in this study.Four-color phenotype combinations were composed of CD10/CD34/CD19 plus another effective marker such as CD38,CD58,CD66c,CD21.The senstitivity of this method was 0.01%,much higher than that of microscopic inspection.In 8 cases,their bone marrow microscopic inspection results showed no remaining leukemic cells;but with flow cytometry,the percentage of leukemic cells were 5.66%,0.36%,1.43%,0.069%,1.55%,2.7%,0.028% and 0.015%,respectively.In risk stratification,all these MRD positive cases were classified into high risk group for relapse and 1 case showed early relapse within 6 months. Conclusion The application of flow cytometry in MRD measurement can significantly improve the sensitivity of detection of remained leukemic cells in childhood B-ALL,and can provide more accurate information on disease progression as well as the efficacy of therapy,thus facilitate future treatment decisions and follow ups.

Acute Leukemia in Children

Acute leukemia is the most common childhood cancer and accounts for 31% of all cancers in children. There are two main types of acute leukemia. The most common is ALL （acute lymphoblastic leukemia） affecting the lymphoid lineage, and the more rare AML （acute myeloid leukemia） affecting the myeloid linage. The intention of this thesis is to follow the course of treatment from the admission to the hospital until the last check up and also see how a child will react to the treatment and side effects in later life. We studied literature and my own case records from the period when I was treated for ALL. From the literature and my case records, we can see that children tolerate treatment quite well. Due to rapid diagnostics and the possibility to give high doses chemotherapy, the overall prognosis appears to be very good. Today, acute leukemias of paediatric patients have a really favourable prognosis. The overall survival rate for ALL is higher than 80% and for AML 65%. So the results are good, but there is still a long way to go before we can be satisfied. To date we do not have a contingency program for children treated for acute leukemia after 18 years of age （neither in Norway or Slovakia） so perhaps this should be a focus point in the future. It could be extended to follow up patients in adulthood in order to monitor late effects that may occur in later life after many years of treatment.

Effect of siRNA targeting Ets2 gene on chemosensitization of human acute monocytic leukemic cell line SHI-1

Objective:This study was to observe the levels of Ets2 mRNA expression in leukemia patients and investigate the effect of small interfering RNA(siRNA)targeting Ets2 gene on sensibility of human acute monocytic leukemic cell line SHI-1 cells to etoposide(VP-16).Methods:Ets2 mRNA levels were determined by reverse transcription polymerase chain reaction(RT-PCR).After the transfection of Ets2 siRNA to SHI-1 cells by electroporation method,qRT-PCR was used to detect Ets2 gene expression in these cells;VP-16-induced apoptosis was investigated by Annexin V-FITC/PI.Results:Est2 mRNA was detectable in SHI-cells.The Est2 expression rate was respectively 10%in 5 healthy volunteers,60%in 5 acute lymphocytic leukemia(ALL)patients,73.68%in 19 acute nonlymphocytic leukemia(ANLL)patients and 100%in 4 chronic myeloid leukemia(CML)patients.The expression levels of Ets2 mRNA were significantly higher in leukemia patients compared with healthy volunteers.It also showed that siRNA targeting Ets2 gene resulted in substantial loss of Ets2 mRNA of SHI-1 cells compared to the control groups.Downregulation of Ets2 gene expression increased SHI-1 cells apoptosis and VP-16-induced apoptosis of SHI-1 cells.Conclusion:The high-level expression of Ets2 transcription factor in leukemia cells were connected with proliferation and anti-apoptosis of leukemia cells.SiRNA mediated Ets2 gene silencing induced cell apoptosis and enhanced in vitro sensitivity to chemotherapy(VP-16)of SHI-1 cells.It speculated the high-level expression of Ets2 may actually be an unfavorable determinant of chemotherapy sensitivity in leukemia.

Clinical variations of serum levels of ferritin,folic acid and vitamin B_(12) in acute leukemia patients

Acute leukemia is one of the most common hematologic malignancies and its exact mechanism of development is unknown yet. In clinical, acute leukemia alw g12 acid are important components of blood cells ays In accompany with abnormal iron balance. Ferritin, folic acid and vitamin this study, we measured variations of serum levels of ferritin （SF）, folic and vitamin B^2 in the acute leukemia patients under different disease stages including first diagnosed stage complete remission （CR） stage and not remission （NR） or relapse stage. It demonstrated that serum SF levels in patients at the first diagnosed stage and NR or relapse stage were significantly higher than the CR stage in acute m leukemia （AML） patients and acute lymphoblastic leukemia （ALL） patients （P〈0.05）. The serum folic acid yelocy levels tic in patients at the first diagnosed stage and NR or relapse stage were significantly lower than the CR stage in AML patients and ALL patients （P〈0.001）. Whereas, serum vitamin B12 levels in AML patients were significantly higher at the first diagnosed stage and NR or relapse stage than the CR stage （P〈0.001）. And it was significantly higher in ALE patients at the NR or relapse stage than at the first diagnosed stage and CR stage （P〈0.05）. There are obvious variations of serum levels of SF, folic acid and vitamin and vitamin B12 and decreased levels B12 offo in acute leukemia patients under different stages. Increased serum levels of SF lic acid may correlate to the active degree of acute leukemia as well as tumor load