MicroRNA signature inBCR–ABL1-like andBCR–ABL1-positive childhood acute lymphoblastic leukemia: similarities and dissimilarities

MicroRNAs and the Diagnosis of Childhood Acute Lymphoblastic Leukemia: Systematic Review, Meta-Analysis and Re-Analysis with Novel Small RNA-Seq Tools

“…Downregulation of miR-125b was reported in four case–control studies (two of them with more than 100 cases), whereas one study reported otherwise [ 51 , 57 , 77 , 83 ]. Some pediatric BCP-ALL cases displayed upregulation of miR-125b: ETV6 - RUNX1 , BCR - ABL1 , ERG -deregulated and t(11;14)(q24;q32) cases [ 29 , 46 , 100 , 101 , 102 , 103 , 104 ]. Although pediatric T-ALL cases are associated with lower miR-125b levels, TLX1 - and TLX3 -driven cases seem to have higher levels compared to other T-ALL cases, and infants with T-ALL have significantly higher miR-125b levels than the respective childhood cases [ 57 , 105 , 106 ].…”

“…Downregulation of miR-196b is a common finding in childhood ALL [ 35 , 54 , 69 , 76 , 78 , 82 , 83 ]. Conversely, upregulation of miR-196b is prominent in pediatric KMT2A -r cases [ 29 , 83 , 100 , 116 ] and in some T-ALL subgroups (such as HOXA -r, PICALM - MLLT10 or CALM - AF10 , inv(7)(p15q35) and SET - NUP214 cases), especially when aberrant expression of HOXA genes is evident [ 20 , 83 , 116 ]. HOXA9 and MEIS1 homeobox oncogenes (adjacent and coexpressed with miR-196b), along with FAS tumor suppressor, are direct targets of miR-196b and drive carcinogenesis in KMT2A -r cases in a bidirectional manner [ 117 ].…”

“…In the same context, infants with T-ALL have been found to have significantly higher miR-223 levels than childhood T-ALL cases, whereas high levels of miR-223 in KMT2A -r cases are apparent [ 79 , 105 ]. Hyperdiploid cases display the highest and TCF3 -r cases (E2A or Transcription Factor 3), the lowest miR-223 levels among BCP-ALL cases [ 29 , 100 ]. Notwithstanding, low expression of plasma miR-223 at admission has been associated with poor prognosis in childhood ALL [ 121 ].…”

“…In the same context, significantly lower levels of let-7b and let-7d compared with controls have been documented in children with KMT2A -r ALL and B-ALL, respectively [ 67 , 69 , 130 ]. Conversely, let-7c, originating from chromosome 21 and clustered with miR-99a, seems to be upregulated in pediatric ALL cases involving fusions in this chromosome, i.e., ETV6 - RUNX1 - and ERG -related cases [ 100 , 101 , 102 ]. Whereas miR-99a is generally downregulated in pediatric ALL, its upregulation in BCP-ALL cases has been identified as the strongest indicator of ETV6 - RUNX1 fusion presence [ 29 , 100 , 101 ].…”

“…Conversely, let-7c, originating from chromosome 21 and clustered with miR-99a, seems to be upregulated in pediatric ALL cases involving fusions in this chromosome, i.e., ETV6 - RUNX1 - and ERG -related cases [ 100 , 101 , 102 ]. Whereas miR-99a is generally downregulated in pediatric ALL, its upregulation in BCP-ALL cases has been identified as the strongest indicator of ETV6 - RUNX1 fusion presence [ 29 , 100 , 101 ]. Restoration of underexpressed levels of miR-99a and miR-100 in ALL cells in vitro resulted in suppression of cell proliferation and increased cell apoptosis after dexamethasone treatment.…”