MiR‐708‐5p is differentially expressed in childhood acute lymphoblastic leukemia but not strongly associated to clinical features

To the Editor: Li and co-workers [1] associated mir-708-5p expression and high-risk B-cell acute lymphoblastic leukemia (ALL) in a small cohort of Chinese patients. Notwithstanding, in our experience, this association is not applicable to patients stratified and treated according to the Brazilian Childhood Leukemia Treatment Group (GBTLI) Protocol. Bone marrow (BM) samples were obtained at diagnosis from 128 consecutive patients assisted from 2002 to 2005 according to GBTLI-ALL-99 protocol [2,3]. In addition, 11 normal BM samples were analyzed. The study was approved by the National Ethics Committee (CONEP. 7329/2009). Complete information about patient features, classification and methodology details were described previously [4]. MiR-708-5p expression was higher compared to control BM samples considering the whole group of patients, however, when stratifying expression levels based on immunophenotype,miR-7085p expression was completely heterogeneous. High expression was only observed in pre-B ALL. In patients with pro-B ALL, expression levels were lower than in pre-B ALL and comparable to normal BM. Comparatively, for T-ALL patients, the expression was significantly lower, compared to B-ALL cells and normal BM (Fig. 1). Considering clinical/biological features, miR-708 expression was higher in patients with age between 12 and 108 months compared to patients with age associated to poor prognosis. Patients with white blood cell (WBC) count at diagnosis <50,000/mm presented higher expression. However, these two associations were not verified when only patients with pre-B-cell ALLwere analyzed, suggesting that these differences might also be associated to T-cell ALL which usually presents higher age and WBC counts. Other features such cytogenetics, minimal residual disease and survival analysis, including risk classification according GBTLI ALL-99, did not present differences. The first description of miR-708-5p in childhood ALL [5] suggested differential expression in ALL subtypes, more specifically, it showed miR-708-5p upregulation in TEL-AML1, BCRABL, E2A-PBX1, hyperdiploid and B-other cases compared with MLL-rearranged and T-ALL patients. These results are in concordance with our observations, where higher miR-708 expression was observed in pre-B than in T-ALL patients. MiR-708-5p differential expression in precursor B-cell ALL samples was also confirmed [1], though contrarily to our results, this microRNA was found hyper-expressed in high-risk pre-B ALL compared to standardand intermediate-risk samples. Differences may be influenced by the treatment protocol (Chinese CCLG-2008 protocol vs. Brazilian GBTLI ALL-99) or reflection of dissimilar sample sizes (34 patients vs. 98 pre-B ALL). It is important to note that according to the CCLG-ALL protocol, only patients with t(9;22), MLL rearrangement or poor treatment response are at high risk [6]. According to Li et al. [1], among the six patients with ALL classified as high risk, two were MLL-AF4(þ) and one BCR-ABL(þ) and the specific miR-708-5p expression levels in these subtypes are known [5]. Considering the low number of patients, and the variability of miR-708-5p expression presented [1] it is reasonable to suggest that miR-708-5p expression may not be associated to risk stratification in other protocols, such as in the GBTLI LLA-99, analyzed in the present study, or the criteria adopted by the American National Cancer Institute (NCI) that include, for instance, age and initial WBC count [7].