Acute myeloid leukemia (AML) is a heterogenous clonal blood disease of a neoplastic origin. There are challenging issues for the intermediate-risk AML group, which is defined as non-homogeneous due to a variety of gene mutations (FLT3, NPM1, CEBPA, etc.), prediction of differential clinical course, relapse risk, and selection of adequate therapy. In this context, a search for new molecular markers with sufficient prognostic value for the relapse risk estimation in AML cases with no detectable cytogenetic abnormalities represents a high-priority task for clinical molecular oncohematology. We analyzed prognostic significance of BAALC (Brain And Acute Leukemia, Cytoplasmic) gene overexpression in 93 AML patients during the posttransplant period, in order to estimate feasibility of BAALC expression level monitoring, to predict the relapse risk, and to evaluate sensitivity and specificity of BAALC gene expression assay, to the purpose of minimal residual disease (MRD) monitoring. BAALC expression was determined by quantitative real-time polymerase chain reaction in fresh bone marrow samples. Patients were dichotomized at BAALC's individual and general cut-off into low and high expressers. We have concluded that BAALC overexpression above both individual and common cut-off levels is recognized as a prognostically significant factor for posttransplant relapse risk estimation, overall survival and relapse-free survival. A more detailed analysis of BAALC as a marker for estimation of therapeutic efficiency was performed. We have also compared its sensitivity to the reference techniques for minimal residual disease monitoring (i.e., qPCR-based detection of chimeric gene transcripts), showing inferior sensitivity of such approach to MRD detection in post-transplant period, at least, for our study group. Serial BAALC monitoring may be recommended for clinical relapse prediction during the post-transplant period in AML patients.
Providencia is a genus of Gram-negative bacteria belonging to the Morganellaceae family. This genus includes nine species (P. stuartii, P. sneebia, P. rettgeri, P. rustigianii, P. heimbachae, P. burhodogranariea, P. alcalifaciens, P. huaxiensis, and P. vermicola) with varying degrees of virulence, capable of infecting humans and insects [1, 2]. For Gram-negative bacteria, the somatic antigen (O-antigen) has become one of the key virulence factors. It is the highly immunogenic part of lipopolysaccharides due to the distal location. O-antigens are characterized by structural heterogeneity, providing varying degrees of inter- and intraspecific virulence. At the genetic level, somatic antigens have an operon structure. Operon genes responsible for the synthesis and transformation of O-polysaccharide are transcribed together. Analysis of O-antigen operon organization determines genes specific for each O-serogroup. It is beneficial for molecular typing of strains and for studies of bacterial evolution. This study focuses on identifying and comparing candidates for O-antigen operons in Providencia species with different levels of virulence. The hypothesis is the presence of an association between the O-antigen operon composition and the bacteria lifestyle. Data processing and analysis are carried out by a pipeline developed by the authors. Pipeline combines five steps of the genome analysis: genome quality evaluation, assembly annotation, operon identification with verification of operon boundaries, and visualization of O-antigen operons. The results reveal previously undescribed O-antigen genes and the changes in the O-antigen operons structure. Among the changes are a transposon insertion leading to tetracycline resistance and the presence of IS elements.
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