Yuping Cheng

The impact of IKZF1 deletion on the prognosis of acute lymphoblastic leukemia: an updated meta-analysis.

BACKGROUND Various studies have reported that IKZF1 deletion (IKZF1-d) is a poor prognostic factor for acute lymphoblastic leukemia (ALL) patients, however they do not agree on the level of significance for this deletion. OBJECTIVE To provide a quantitative assessment of this correlation, an updated meta-analysis of cohort studies was performed to derive a more precise estimation of the prognostic significance of IKZF1-d. METHODS Relevant studies were identified in PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang databases until January 31, 2014. A total of 15 published studies including 5021 patients were eligible for this meta-analysis. Combined hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with random-effects model. RESULTS Combined hazard ratios suggested that IKZF1 deletion (IKZF1-d) had an unfavorable impact on event-free survival (EFS) (HR=2.32, 95%CI: 1.97-2.74) and overall survival (OS) (HR=2.56, 95%CI: 1.75-3.74) in patients with ALL. The significant role of IKZF1-d in the prognosis of ALL was also observed among different subgroups stratified by statistical methodology, ethnicity, age, detection method, risk group and duration of follow up. CONCLUSIONS The findings from this meta-analysis suggest that IKZF1 deletion can be used to serve as an independent predictive factor in patients with ALL.

Novel Mutations in the UNC13D Gene Carried by a Chinese Neonate with Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) in different ethnicities has been described in the literature, but few cases in patients of Chinese descent have been reported. Here, we describe the case of a Chinese neonate presenting with HLH carrying novel, compound heterozygous mutations of the UNC13D gene, including [c.2295_2298delGCAG, p.Glu765Aspfs*27] in exon 23, c.-250C>T, c.1+30G>A, c.279C>T, c.888G>C, c.18+36A>G, c.20-48T>C, c.1977C>T, c.2296C>T, c.24-46C>T, c.26-9_26-8insC, c.2599A>G, c.28+48C>T and c.3198A>G, some of which have not been reported in the literature. Cytokine profile analyses were performed in this patient, and the results were consistent with our previous findings in HLH patients. Cytokine profile monitoring may be helpful in differentiating among various clinical phases of HLH.

Prognostic significance of cytokine receptor-like factor 2 alterations in acute lymphoblastic leukemia: a meta-analysis

BackgroundCytokine receptor-like factor 2 (CRLF2) has been shown to play a role in the pathogenesis of acute lymphoblastic leukemia (ALL). Studies have examined the relationship between CRLF2 alterations such as over-expression or deregulation and clinical outcome in childhood ALL, but the results are conflicting. This meta-analysis aimed to explore the association between CRLF2 alterations and survival of pediatric patients with ALL.MethodsElectronic databases updated to March 2014 were searched for relevant studies. A meta-analysis was made of twelve studies including 5945 patients to evaluate the prognostic significance of CRLF2 alterations on survival in childhood ALL. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across the studies using a fixed-effects model.ResultsCRLF2 over-expression in childhood ALL was associated with poor prognosis in terms of relapse-free survival (RFS; HR=1.70, 95% CI=1.28–2.24, P=0.000), event-free survival (EFS; HR=1.78, 95% CI=1.05–3.01, P=0.032), and overall survival (OS; HR=2.28, 95% CI=1.42–3.65, P=0.001). The combined data also suggested that CRLF2 deregulation in childhood ALL was correlated with poor EFS (HR=1.95, 95% CI=1.46–2.61, P=0.000), RFS (HR=2.20, 95% CI=1.53–3.18, P=0.000), and OS (HR=1.89, 95% CI=1.24–2.87, P=0.003). Subgroup analysis on multivariate HRs showed that CRLF2 deregulation independently predicted a poor prognosis for childhood ALL.ConclusionsThe present meta-analysis reveals that both CRLF2 over-expression and deregulation are associated with poor prognosis in pediatric patients with ALL.

The ratio of absolute lymphocyte count at interim of therapy to absolute lymphocyte count at diagnosis predicts survival in childhood B-lineage acute lymphoblastic leukemia

Absolute lymphocyte count (ALC) after therapy has been reported to be an independent prognostic factor for clinical outcome in leukemia. This study mainly analyzed ALC at interim of therapy on day 22 (ALC-22) and the ratio of ALC-22 to ALC at diagnosis (ALC-0) on the impact of survival and the relation of ALC to lymphocyte subsets in 119 pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients. Univariate analysis revealed that ALC-22/ALC-0 ratio <10% was significantly associated with inferior overall survival (OS) (hazard ratio (HR)=12.24, P=0.0014) and event-free survival (EFS) (HR=3.3, P=0.0046). In multivariate analysis, ALC-22/ALC-0 ratio remained an independent prognostic factor for OS (HR=6.92, P=0.0181) and EFS (HR=2.78, P=0.0329) after adjusting for age, white blood cell (WBC) count and minimal residual disease (MRD) status. A Spearman correlation test showed that CD3+ T cells had a negative correlation with ALC-0 (r=-0.7204, P<0.0001) and a positive correlation with ALC-22 (r=0.5061, P=0.0071). These data suggest that ALC-22/ALC-0 ratio may serve as a more effective biomarker to predict survival in pediatric B-ALL and ALC is mainly associated with CD3+ T cells.

Successful construction and stable expression of an anti-CD45RA scFv–EGFP fusion protein in Chinese hamster ovary cells

CD45RA has been found highly expressed on leukemia cells and may be a potential target of the disease. In this study, an anti-CD45RA single-chain antibody fragment (scFv3A4) was genetically linked to the N terminus of the enhanced green fluorescent protein (EGFP) to generate a scFv3A4-EGFP fusion protein. The scFv3A4-EGFP with a molecular weight of 57kDa was stably expressed and secreted from the transfected CHO cells through the ER/Golgi-dependent pathway. The fusion protein was soluble in the culture supernatant and the yield was 1350μg/L. Flow cytometry analysis showed that the scFv3A4-EGFP had the same binding site and a very similar reactivity pattern with its parental murine monoclonal antibody (mAb) 3A4. Furthermore, comparing to conventional labeled 3A4-FITC antibody, the scFv3A4-EGFP was more resistant to illumination and more suitable for immunofluorescence histology (IFH) detection. Therefore, the scFv3A4-EGFP fusion protein can be a powerful tool to investigate the targeting of CD45RA on leukemia cells, biological activity of the target and possibly for the genetic manipulation of the antibody.

Overexpression of lymphoid enhancer‐binding factor‐1 (LEF1) is a novel favorable prognostic factor in childhood acute lymphoblastic leukemia

Lymphoid enhancer‐binding factor‐1 (LEF1) is a target gene and central mediator of the Wnt signaling pathway. High LEF1 expression has been reported as a prognostic marker in several types of hematologic malignancies of adult patients.

High expression of Midkine (MK) indicates poor prognosis in childhood acute lymphoblastic leukemia

Objectives: Midkine (MK) expression has been reported to be correlated with the poor prognosis of patients with various tumors. However, there are no data available about the prognostic value of MK expression in childhood acute lymphoblastic leukemia (ALL). Methods: In this study, MK mRNA expression was determined by real-time polymerase chain reaction in 120 childhood ALL and 30 healthy volunteers. Patients were dichotomized at the median value and divided into two groups: MKlow group and MKhigh group. Results: MKhigh patients had higher white blood cell counts, higher peripheral blood blasts percentages, and higher minimal residual disease levels than MKlow patients. Moreover, the MK gene was expressed significantly higher in patients with relapsed ALL than in patients who maintained complete remission or at diagnosis. MKhigh patients harbored inferior relapse-free survival (RFS, P = 0.047) and overall survival (OS, P = 0.022) than MKlow patients, and high expression of MK was found to be independently predictive of inferior OS (P = 0.032) but not RFS (P = 0.077) in the overall cohort. Conclusion and discussion: MK high expression is an independent adverse prognostic factor in childhood ALL. Its level may be incorporated into an improved risk classification system for ALL and suggest the need of alternative regimens.

Association between NOD2 single nucleotide polymorphisms and Grade III–IV acute graft-versus-host disease: A meta-analysis

Abstract Objectives The effects of NOD2 single nucleotide polymorphisms (SNPs) on Grade III–IV acute graft-versus-host disease (aGVHD) risk are somewhat contradictory in different studies. The aim of the meta-analysis was to clarify the effects of NOD2 SNPs on the incidence of Grade III–IV aGVHD. Methods We searched PubMed, EMBASE, Web of SCIENCE, WanFang and Chinese National Knowledge Infrastructure (CNKI) databases to collect eligible publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between NOD2 polymorphisms and Grade III–IV aGVHD risk. Results A total of nine studies from eight publications met the inclusion criteria and were included in this meta-analysis. Patient NOD2 SNPs were not associated with aGVHD risk. A tendency of higher risk to develop Grade III–IV aGVHD was found in patients with pairs NOD2 SNPs. Subgroup analyses showed that pairs NOD2 SNPs were associated with Grade III–IV aGVHD in the Caucasian population and in identical sibling donors (IS), but not in matched unrelated donors (MUD). In patients who received hematopoietic stem cell transplantation (HSCT) with T-cell depletion and gut decontamination, there was still an association between pairs NOD2 SNPs and Grade III–IV aGVHD risk. Conclusions Our meta-analysis suggests that pairs NOD2 SNPs, not patient NOD2 SNPs, may be associated with Grade III–IV aGVHD risk, especially in the Caucasian population. It is also indicated that in pairs NOD2 polymorphisms group, patients who receive HSCT from IS may experience higher risk of Grade III–IV aGVHD.