Down-Regulation of MicroRNA-143 and -145 in Childhood B-Lineage Acute Lymphoblastic Leukemia at Initial Diagnosis and in Relapse but up-Regulated When in Remission

Abstract

Inappropriate expression of microRNAs (miRNAs) is strongly associated with leukemogenesis. miRNAs (miRs)-143 and -145, previously shown to be reduced in colon cancers, have been demonstrated recently to be down-regulated in B-cell malignancies including chronic lymphoblastic leukemia, B-cell lymphoma, Burkitt’s lymphoma. In this study, we determined the role of miR-143 and miR-145 in childhood leukemia treated by the standard TPOG (Taiwan Pediatric Oncology Group)-2002 protocols approved for treatment of patients in Taiwan. Ten patients with childhood B-lineage ALL and four ALL leukemia cells lines including REH (CRL-8286TM), CCRF-SB (CCL-120TM), RS4 (CRL-1873TM), and SUP-B15 (CRL-1929) were measured for the miRNA expression using a TagMan quantitative RT-PCR method. Our results showed that miR-143 and miR-145 were both down-regulated 0.09 and 0.19 times individually (n= 13, p <0.001 and p = 0.011) in mononuclear cells in bone marrow of newly-diagnosed and relapsed samples in comparison with the same cell types of remission samples (n=16). To examine possible suppressive functions of miR-143 and miR-145 with respect to cell growth, the REH cells were used for expression with precursor form and mature form miR-143 and miR-145, and subsequently measured for cell growth rate. Preliminary results showed that the two miRNAs did not alter the growth rate of the REH over-expressing either miRNA. Taken together, we have identified miR-143 and miR-145 as biomarkers that may differentiate malignant and normal B cells. miR-143 and miR-145 may contribute to leukemogenesis in childhood B-lineage ALL by new yet to be defined mechanisms.

Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia

“…The tumor suppressor role of miR-143-3p has not been reported thus far in the context of T-ALL. However, it has been suggested in several cancer types, including solid tumors [ 10 ], myeloid and B-cell malignancies [ 11 , 12 , 13 ]. In acute lymphoblastic leukemia originating from B-cell precursors (BCP-ALL), miR-143 was shown to be downregulated in diagnostic and relapse samples as compared to remission samples [ 11 ].…”

“…However, it has been suggested in several cancer types, including solid tumors [ 10 ], myeloid and B-cell malignancies [ 11 , 12 , 13 ]. In acute lymphoblastic leukemia originating from B-cell precursors (BCP-ALL), miR-143 was shown to be downregulated in diagnostic and relapse samples as compared to remission samples [ 11 ]. The authors tested the hypothesis on the tumor suppressor role of this miRNA by cell growth assays in REH cells upon miRNA overexpression, yet no impact on growth rate was observed in this particular B-ALL cell line.…”