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Abstract: Objective: To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. Methods: Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. Results: The Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. bovis and M. africanum strains from the four loci. Conclusion: We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing. [Copyright &y& Elsevier]

Background: Although leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes. Methods: This study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19+CD10− pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children's Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed. Results: KMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1+ patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively). Conclusions: Pediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required. [ABSTRACT FROM AUTHOR]