Simultaneous changes in expression levels of BAALC and miR-326: a novel prognostic biomarker for childhood ALL

Abstract

Objective Multidrug resistance and consequent relapse are two major obstacles for treating children with acute lymphoblastic leukemia, the most frequent childhood malignancy. MicroRNAs have potential regulatory roles in response to chemotherapy. The goal of this study was to determine the microRNA that may have effects on the expression level of brain and acute lymphoblastic leukemia (BAALC) and to investigate the in vitro and ex vivo association between their expression levels. Methods In silico tools were utilized to determine a putative miRNA targeting BALLC. Quantitative real-time polymerase chain reaction was used to investigate expression levels of BAALC and its predicted microRNA, miR-326, in bone marrow samples of 30 children with acute lymphoblastic leukemia and 13 controls, in addition to the resistant and parental CCRF-CEM cell lines. To assess the status of response to therapy, minimal residual disease was measured using single-strand conformation polymorphism. Results MiR-326 was selected due to the strong possibility of its interaction with BAALC according to the obtained in silico results. Statistical analysis showed a significant downregulation of miR-326 and overexpression of BALLC in drug-resistant acute lymphoblastic leukemia cell line and patients compared with the parental cell line and drug-sensitive patients, respectively (P = 0.015, 0.005, 0.0484 and 0.0005, respectively). The expression profiles of miR-326 and BAALC were inversely correlated (P = 0.028). Conclusions The results introduced the inversely combined expression levels of miR-326 and BAALC as a novel, independent prognostic biomarker for pediatric acute lymphoblastic leukemia (P = 0.007). Moreover, bioinformatics data showed a possible regulatory role for miR-326 on BAALC mRNA, which may possibly contribute to the development of drug resistance in patients with childhood acute lymphoblastic leukemia.

RNA-seq–based miRNA signature as an independent predictor of relapse in pediatric B-cell acute lymphoblastic leukemia

“…Hereafter, we refer to this subgroup with a distinct miRNA expression profile as the miR-low cluster (MLC). Notable differentially expressed miRNAs in the MLC included tumor suppressive (eg, miR-26b, 20 miR-101, 21 miR-29, miR-142, 22 miR-146b, 23 and miR-326 24 ) and oncogenic (eg, miR-130b 25 and miR-92a 26 ) miRNAs linked to leukemia. Consecutive 2-step unsupervised consensus clustering of the MLC and non-MLC group identified 4 clusters respectively, which generally clustered together with well-known subtypes ( supplemental Figure 2 C), further highlighting the distinct features of the aberrant miRNA expression profile identified in the MLC.…”

Diagnostic significance of dysregulated miRNAs in T-cell malignancies and their metabolic roles

“…As high expression of miR-30 in breast cancer is associated with better survival and prognosis ( 58 ), its low expression in T-ALL may possibly resemble poor survival, which requires further investigation. Lower expression of miR-326, along with high expression of BAALC (brain and acute lymphoblastic leukemia cytoplasmic protein), is associated with poor survival, especially in children, along with leukemogenesis, shorter survival, resistance to therapy, and MRD (minimal residual disease) ( 46 ). There are other miRNAs, for instance, miR-16, which, despite having a nonsignificant overexpression in T-ALL, gave better 1-year survival rates as high as 50% in patients having comparatively higher levels of miR-16 ( 28 ).…”

MicroRNA as a Prognostic and Diagnostic Marker in T-Cell Acute Lymphoblastic Leukemia

“…Its overexpression is associated with poor outcomes in children with ALL, therapy resistance, leukemogenesis, shorter survival, and MRD. In the study, they suggest that the high expression of BAALC combined with low expression of miR-326 may be an independent prognostic marker in children with ALL due to the characteristic expression profile in MRD and relapsed pediatric patients [ 58 ].…”