CD7 expression and its prognostic significance in acute myeloid leukemia patients with wild-type or mutant CEBPA / 中华血液学杂志

Objective@#To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7+ in AML patients with wild-type (WT) or mutant-type (MT) CEBPA.@*Methods@#The clinical data of 298 newly diagnosed non-M3 AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7+ and CD7- patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7+ group by Kaplan-Meier method.@*Results@#In CD7+ group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7- group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7+ group comparing to those of CD7- group in AML patients with wild type CEBPA. There were no statistical difference between CD7+ group and CD7- group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7+ group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7+-CEBPA MT group, CD7- and CD7+-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) .@*Conclusion@#The CEBPA mutation rate was higher in CD7+ AML patients then that of CD7- patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.

Expression of gene and its prognostic value in patients with acute myeloid leukemia / 浙江大学学报·医学版

OBJECTIVE@#To investigate the expression of Wilms'tumor 1 () gene in patients with acute myeloid leukemia (AML), and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1() and Fms-like tyrosine kinase 3-internal tandem duplication ().@*METHODS@#One hundred and sixty-seven newly diagnosed AML patients(exclued M3 type) were enrolled in this study. The survival of patients were analyzed with Kaplan-Meier method. The clinical data, laboratory findings and the survival of patients were analyzed and compared between patients with high expression (high- group) and those with low expression (low- group), as well as among the patients with or wild type and mutants.@*RESULTS@#The overall response rates (ORR) in high- and low- groups were 65.9% (83/126) and 95.1% (39/41), respectively (0.05). In patients with wild type, the high- group had inferior ORR and 2-y OS rate (all 0.05).@*CONCLUSIONS@# gene overexpression indicated poor prognosis of AML patients; the patients with decreased gene expression ≥ 1 log after the first induction therapy show better prognosis than those with<1 log. The gene expression level at diagnosis can be used as an unfavorable prognostic factor for AML patients with or wild types.

Roles of CCAAT enhancer binding protein α in acute myeloblastic leukemia / 浙江大学学报·医学版

The CCAAT enhancer binding protein α (C/EBP α:p42 and p30),which encoded by CCAAT enhancer binding protein α () gene,plays a pretty crucial role in the regulation of myeloid hematopoiesis.The disorder of CEBPA gene expression is an pivotal mechanism of acute myeloid leukemia (AML). The result of uncontrolled expression of C/EBP α gene is the over-expression of p30 and the incomplete loss of p42, both of which contribute to the occurrence of AML. Restoring the expression ratio of C/EBP α such as over-expression of p42 or blocking the carcinogenic pathway of p30 seems to be important for the treatment of AML caused by such causes. In order to better guide medical decision-making, this article reviews research progress on C/EBPα in the pathogenesis of AML.

Aberrant DNA methylation and its targeted therapy in acute myeloid leukemia / 浙江大学学报·医学版

The occurrence and development of acute myeloid leukemia (AML) is not only related to gene mutations, but also influenced by abnormal epigenetic regulation, in which DNA methylation is one of the most important mechanisms. Abnormal DNA methylation may lead to the activation of oncogene and the inactivation of tumor suppressor gene, resulting in the occurrence of leukemia. The mutations of DNA methylation enzymes associated with AML may have certain characteristics. The AML with recurrent cytogenetic abnormalities is also related to abnormal methylation. Some fusion genes can alter DNA methylation status to participate in the pathogenesis of leukemia. In addition, chemotherapy drug resistance in patients with AML is associated with the change of gene methylation status. Considering the reversibility of the epigenetic modification, targeted methylation therapy has become a hotspot of AML research.

Short-term effects of hemogram in healthy donors after peripheral blood stem cell collection / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the short- term effects of hemogram in donors after peripheral blood stem cell（PBSC）collection and donors' tolerance.</p><p><b>METHODS</b>A total of 166 related allogeneic donors were selected from The First Affiliated Hospital of Medical School of Zhejiang University between January 2013 and December 2014, including 86 male and 80 female. All donors accepted granulocytecolony- stimulating factor（G-CSF）5-10 μg·kg⁻¹·d⁻¹ until collection finished and were measured by blood cells count before and after PBSC collection.</p><p><b>RESULTS</b>After PBSC collection, the hemoglobin level decreased from 145（94-181）g/L to 138（93-167）g/L, and the platelet counts decreased in all donors from 231（105- 490）× 10⁹/L to 95（39- 210）× 10⁹/L. The amount of hemoglobin contamination in collection products was weak correlated with the decreased hemoglobin in peripheral blood（r=0.297, P=0.017）, and the platelet contamination was high correlated with that decreased in peripheral blood（r=0.719, P<0.001）. The decline of hemoglobin level after twice PBSC collection was of no significant difference between four groups in different ages（P≥0.05）. The decline of platelet counts was out of a significant difference（P> 0.05）. In addition, the decline of hemoglobin level after once and twice PBSC collection was of a significant difference between four groups in different body mass index（BMI）（P=0.003 and P<0.001）, especially in thinner group with obvious decrease. But the decline of platelet counts was out of a significant difference （P>0.05）.</p><p><b>CONCLUSION</b>The hemoglobin level decreased mildly in healthy allogeneic hematopoietic stem cell donors after PBSC collection and it is better to adjust parameters every time to ensure their safety for thinner donors. However, it will increase the risk of platelet decline, which is unrelated with ages and BMI and can be tolerated.</p>

Expression and clinical significance of anti-apoptosis gene, survivin, in acute leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the correlation between expression of surviving gene in acute leukemic cells and its clinical effects.</p><p><b>METHODS</b>By using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique, surviving gene expression in 50 previously untreated acute leukemia (AL) patients was analysed. The apoptosis of primary leukemia cells cultured in vitro was assayed with terminal deoxyribonucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL).</p><p><b>RESULTS</b>Surviving gene expression levels in cells of AL patients at diagnosis were significantly higher than that in normal bone marrow mononuclear cells (MNCs) (82.0% vs 33.3%, P < 0.05). The expression level was higher in ALL cells than in ANLL cells (89.5% vs 75.0%). Among 22 cases of ANLL, bone marrow remission (BMR) rate was higher in surviving gene negative expression cells from patients accepted a course of chemotherapy than in positive expression cells (83.3% vs 25.0%, P = 0.023). Among 13 ANLL patients received a course of HA regimen chemotherapy, the BMR was higher in patients surviving mRNA negative expression cells than in positive cells (100.0% vs 27.3%). Patients with surviving/beta-actin ratio>0.6 attained lower BMR.</p><p><b>CONCLUSION</b>Higher expression level of surviving mRNA in AL cells may be one of the reasons that leukemic cells are insensitive to chemotherapy.</p>

Preparation of sustained-release dropping pills of total glucosides in Radix Paeoniae Alba / 中草药

Objective To optimize the formulation in preparation of dropping pills with total glucosides in Radix Paeoniae Alba and evaluate its accumulative release percentage in vitro.Methods With the hardness,roundness,and adhesion as the evaluation,orthogonal design was conducted.With dissolution rate of 12 h as the indices,according to the uniform design,the optimum coating formulation of Eudragit RL and RS was established.Results The dropping pills met the criterion of formulation,and the preparation release met the characteristics of the sustained release of the first order kinetics.Conclusion The optimal formulation is simple,which provides the basis for further development of new preparations of total glucosides in Radix Paeoniae Alba.