Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes.

Background: Overexpression of the cytokine receptor-like factor 2 (CRLF2) gene is the most common feature in the Philadelphia chromosome (Ph)-like subtype of B-cell acute lymphoblastic leukemia (B-ALL). However, the predictive value of CRLF2 overexpression for the prognosis of pediatric B-ALL patients remain controversial. The molecular mechanisms that upregulate CRLF2 expression level in patients has not been fully elucidated. Methods: In this study, the prognostic impact of CRLF2 expression level on molecular types of B-ALL in pediatric patients from Zhujiang Hospital (n = 111) was retrospectively analyzed. Youden index analysis was used to categorize CRLF2 expression into 3 groups, and these categories more precisely described the differences in the prognosis of patients with varying expression levels of CRLF2 in both the Zhujiang Hospital cohort and the TARGET cohort. Results: We used the Zhujiang Hospital cohort as a discovery cohort to determine the cutoff value of CRLF2 expression. CRLF2-high patients accounted for approximately 6%. In addition, the percentage of bone marrow blast cells and initial white blood cell count in CRLF2-high patients were higher than those in CRLF2-low patients, and MRD turned negative slower. The results were validated in the TARGET cohort and indicated that CRLF2 overexpression could be subdivided by CRLF2 expression levels into 2 categories: CRLF2-high with a poor survival and CRLF2-medium with a good OS and EFS. Such heterogeneity was attributed to the different molecular mechanisms leading to CLRF2 upregulation, where the CRLF2 overexpression level was high in Ph-like B-ALL and medium in high hyperdiploid B-ALL. Conclusion: This study highlights the importance of the molecular mechanisms of the upregulation of CRLF2 expression in predicting the prognosis of pediatric B-ALL patients.

A new pattern-based method for identifying recent HIV-1 infections from the viral env sequence.

The long asymptomatic stage of HIV infection poses a great challenge in identifying recent HIV infections. This is a bottleneck for monitoring HIV epidemic trends and evaluating the effectiveness of national AIDS control programs. Several serological methods were used to address this issue with some success. Because of high false-positive rates in patients with advanced infection or in ART treatment, UNAIDS still hesitates to recommend their use in routine surveillance. We developed a new pattern-based method for measuring intra-patient viral genetic diversity for determination of recent infections and estimation of population incidence. This method is verified by using several datasets (424 subtype B and 77 CRF07_BC samples) with clearly identified HIV-1 infection times. Pattern-based diversities of recent infections are significantly lower than that of chronic ones. With larger window periods varying from 200 to 350 days, a higher accuracy (90%-95%) not affected by advanced disease nor ART treatment could be obtained. The pattern-based genetic method is supplementary to the existing serology-based assays, both of which could be suitable for use in low and high epidemic regions, respectively.