Prognostic significance of BAALC overexpression in patients with AML during the posttransplant period

Abstract

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.

Clinical significance of BAALC overexpression for predicting post-transplant relapses in acute myeloid leukemia

“…The BAALC and WT1 expression levels for the previously discussed AML patients [23] were assessed in the context of our recent findings. As shown in Fig.…”

“…Total mRNA extraction from fresh bone marrow samples, its reverse transcription and quantitative estimation of the BAALC gene expression level were performed as previously described [23]. Basic control time points for bone marrow sampling were as follows: at diagnosis (e.g., D-80), just before allo-HSCT, prior to the conditioning (D0) and after allo-HSCT, i.e.…”

Quantitative study of BAALC- and WT1-expressing cell precursors in the patients with different cytogenetic and molecular AML variants treated with Gemtuzumab ozogamicin and hematopoietic stem cell transplantation

“…Cytogenetic studies were carried out using standard criteria to detect chromosome aberrations. Simultaneous serial measurements of BAALC and WT1 gene expressions levels were performed with quantitative real-time polymerase chain reaction (qRT-PCR), according to earlier described technique [20]. In brief, RNA was isolated from the fresh bone marrow samples by guanidine-phenol-chloroform extraction ("Ribozol-DF" kit reagent, InterLabService, Russia), according to the manufacturer's instructions.…”

Clinical Value of miR-3151 Overexpression in Synergistic Interaction with BAALC Host Gene in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

“…1, А). Для оценки же клинического значения гиперэкспрессии BAALC в группах пациентов с miR-3151-позитивным и miR-3151-негативным статусом был применен пороговый уровень 60 % [13,14].…”