Glycolysis is a main catabolic pathway of glucose metabolism, accompanied by ATP synthesis. More than 30 enzymes are involved in glycolysis, and genes that encode them can be considered housekeeping genes due to the high conservatism and evolutionary antiquity of the process. We studied the expression of these genes in kidney papillary cancer and planocellular lung cancer via the bioinformatic analysis of transcriptome database and method of quantitative real time PCR. Quantitative analysis of mRNA level demonstrated that only a part ofgenes that encode glycolysis enzymes maintain relatively stable mRNA level, including the HK1, ADPGK, GPI, PGK1, and PKM2 genes in kidney papillary cancer and the ADPGK, ALDOA, GAPDH, PGK1, BPGM, ENO1, and PKM2 genes in planocellular lung cancer. The frequent increase in the mRNA expression of PFKP, ALDOA, and GAPDH genes in kidney cancer, as well as the GPI gene in lung cancer, were detected for the first time by real time PCR. For other genes, their differential expression was demonstrated; the cases of both a decrease and increase in the mRNA level were detected. Thus, several genes that can be used as control genes in transcriptome analysis by real time PCR in kidney and lung cancer, as well as a number of differentially expressed genes that can be potential oncomarkers, were identified.
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.
This article presents data demonstrating frequent BAALC hyperexpression, also in combination with WT1 hyperexpression, in children and adults with acute myeloid leukemia (AML). Treatment included allogeneic hematopoietic stem cell transplantation. The analysis of serial measurements of BAALC and WT1 expression level in 50 AML patients (37 adults and 13 children) showed that the increased BAALC expression is more common in patients with M1, M2, M4, and M5 FAB variants of AML with equal frequency in adults and children. Furthermore, the increased BAALC expression was rather common in combination with the increased WT1 expression, which predicted poorer prognosis. Since BAALC expression level in AML patients is closely related to AMLproducing progenitor cells of leukemia hemato poiesis, a serial study of this phenomenon off ers insights into the role of these cells in emergence and development of post-transplantation relapses, which is of both theoretical and practical importance.
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