Low Expression of miR-18a as a Characteristic of Pediatric Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia (ALL) occurs in both adults and children but the response to chemotherapy and survival is significantly worse in the adults. We aimed to study whether the expression of immune system-associated miRNAs would differ between adult and pediatric patients with ALL at the time of diagnosis. Materials and Methods: Inflammation-associated miRNA analysis was performed in 19 adults and 79 pediatric patients with ALL and involved miR-10, miR-15, miR-16, miR-17-92 cluster, miR-33, miR-146a, miR-150, miR-155, miR-181a, miR-222, miR-223, and miR-339. MiRNAs were first analyzed by miRNA microarray and thereafter validated by qRT-PCR. Sufficient RNA for qRT-PCR was available for 42 pediatric and 19 adult patients. Results: Of the studied miRNAs, only miR-18a differed significantly in microarray analysis between adult and pediatric ALL, being lower in children (FC, −3.74; P, 0.0037). Results were confirmed by qRT-PCR (down-regulated in pediatric patients, P 0.003161). The other members of the miR-17-92 cluster did not differ significantly. Conclusions: Pediatric and adult patients with ALL have remarkably similar patterns of immune-cell–associated miRNAs in their bone marrow at diagnosis. However, the low expression of miR-18a in pediatric ALL is interesting and demands further study.

[1]  K. Moore,et al.  MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. , 2015, The Journal of clinical investigation.

[2]  J. Downing,et al.  Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  M. Abdullah,et al.  Increased regulatory T cells in acute lymphoblastic leukaemia patients , 2015, Hematology.

[4]  P. Sethupathy,et al.  miR-182 and miR-10a Are Key Regulators of Treg Specialisation and Stability during Schistosome and Leishmania-associated Inflammation , 2013, PLoS pathogens.

[5]  J. Roganović Acute Lymphoblastic Leukemia in Children , 2013, Journal of Indian Academy of Oral Medicine and Radiology.

[6]  R. Gay,et al.  Tumor necrosis factor α-induced microRNA-18a activates rheumatoid arthritis synovial fibroblasts through a feedback loop in NF-κB signaling. , 2013, Arthritis and rheumatism.

[7]  D. Grandér,et al.  Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric acute lymphoblastic leukemia , 2012, Leukemia & lymphoma.

[8]  S. Knuutila,et al.  Integrated Analysis of Gene Copy Number, Copy Neutral LOH, and microRNA Profiles in Adult Acute Lymphoblastic Leukemia , 2012, Cytogenetic and Genome Research.

[9]  S. Knuutila,et al.  MicroRNA microarrays on archive bone marrow core biopsies of leukemias--method validation. , 2011, Leukemia research.

[10]  C. Distelhorst,et al.  Glucocorticoid-mediated repression of the oncogenic microRNA cluster miR-17~92 contributes to the induction of Bim and initiation of apoptosis. , 2011, Molecular endocrinology.

[11]  David Baltimore,et al.  Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses , 2010, Cell.

[12]  S. Knuutila,et al.  Unique microRNA profile in Dupuytren's contracture supports deregulation of β-catenin pathway , 2010, Modern Pathology.

[13]  Andrea Califano,et al.  The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. , 2010, Cancer cell.

[14]  Hui Zhou,et al.  Genome-Wide Analysis of Small RNA and Novel MicroRNA Discovery in Human Acute Lymphoblastic Leukemia Based on Extensive Sequencing Approach , 2009, PloS one.

[15]  M. Lotze,et al.  Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1 , 2009, Proceedings of the National Academy of Sciences.

[16]  M. D. Boer,et al.  Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia , 2009, Leukemia.

[17]  Ryan M. O’Connell,et al.  MicroRNAs: new regulators of immune cell development and function , 2008, Nature Immunology.

[18]  Rudolf Jaenisch,et al.  Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters , 2008, Cell.

[19]  O. Kirak,et al.  Regulation of progenitor cell proliferation and granulocyte function by microRNA-223 , 2008, Nature.

[20]  N. Rajewsky,et al.  MiR-150 Controls B Cell Differentiation by Targeting the Transcription Factor c-Myb , 2007, Cell.

[21]  Carlo M. Croce,et al.  MicroRNAs 17-5p–20a–106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation , 2007, Nature Cell Biology.

[22]  N. Rajewsky,et al.  Regulation of the Germinal Center Response by MicroRNA-155 , 2007, Science.

[23]  Mark M. Davis,et al.  miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection , 2007, Cell.

[24]  G. Gustafsson,et al.  Treatment outcome in young adults and children >10 years of age with acute lymphoblastic leukemia in Sweden , 2006, Cancer.

[25]  D. Baltimore,et al.  NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses , 2006, Proceedings of the National Academy of Sciences.

[26]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[27]  P. Sonneveld,et al.  Significant difference in outcome for adolescents with acute lymphoblastic leukemia (ALL) treated on pediatric versus adult ALL protocols. , 2003 .

[28]  J. Cayuela,et al.  Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  C. Schiff,et al.  Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification , 2000, Leukemia.