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Tran N.-T.,University of Alabama at Birmingham | Su H.,University of Alabama at Birmingham | Khodadadi-Jamayran A.,University of Alabama at Birmingham | Zhang L.,University of Alabama at Birmingham | And 6 more authors.
EMBO Reports | Year: 2016

Antisense RNAs regulate the transcription and translation of the corresponding sense genes. Here, we report that an antisense RNA, AS-RBM15, is transcribed in the opposite direction within exon 1 of RBM15. RBM15 is a regulator of megakaryocyte (MK) differentiation and is also involved in a chromosome translocation t(1;22) in acute megakaryocytic leukemia. MK terminal differentiation is enhanced by up-regulation of AS-RBM15 expression and attenuated by AS-RBM15 knockdown. At the molecular level, AS-RBM15 enhances RBM15 protein translation in a CAP-dependent manner. The region of the antisense AS-RBM15 RNA, which overlaps with the 5′UTR of RBM15, is sufficient for the up-regulation of RBM15 protein translation. In addition, we find that transcription of both RBM15 and AS-RBM15 is activated by the transcription factor RUNX1 and repressed by RUNX1-ETO, a leukemic fusion protein. Therefore, AS-RBM15 is a regulator of megakaryocyte differentiation and may play a regulatory role in leukemogenesis. © 2016 EMBO.

Ehrlich P.F.,University of Michigan | Hamilton T.E.,Dana-Farber Cancer Institute | Gow K.,Seattle Childrens Hospital Seattle | Barnhart D.,Primary Childrens Medical Center Salt Lake | And 11 more authors.
Pediatric Blood and Cancer | Year: 2016

Background: The purpose of this study was to evaluate the frequency and characteristics of surgical protocol violations (SPVs) among children undergoing surgery for renal tumors who were enrolled on the Children's Oncology Group (COG) renal tumor biology and classification study AREN03B2. Methods: AREN03B2 was opened in February 2006, and as on March 31, 2013, there were 3,664 eligible patients. The surgical review forms for 3,536 patients with unilateral disease were centrally reviewed for SPVs. The frequency, type, number of violations, institutional prevalence, and quartiles for SPVs were assessed. Results: Of the 3,536 patients, there were a total of 505 with at least one SPV (564 total SPVs reported), for an overall incidence of 14.28%. The types of SPVs included a lack of lymph node sampling in 365 (64.7%), avoidable spill in 61 (10.8%), biopsy immediately before nephrectomy in 89 (15.8%), an incorrect abdominal incision in 32 (5.7%), and unnecessary resection of organs in 17 (3.0%). The SPVs occurred in 163 of 215 participating institutions (75.8%). For centers with at least one SPV, the mean number of SPVs reported was 3.10 ± 2.39 (mean ± standard deviation). The incidence of protocol violation per institution ranged from 0 to 67%. Centers with an average of ≤1 case/year had an incidence of SPVs of 12.2 ± 3.8%, those with an average of >1 to <4 cases/year had an incidence of SPVs of 16.4 ± 3.6%, and those with an average of ≥4 cases/year had an incidence of SPVs of 12.6 ± 5.5% (P > 0.05). Conclusions: SPVs that potentially result in additional exposure to chemotherapy and radiation therapy are not uncommon in children undergoing resection of renal malignancies. © 2016 Wiley Periodicals, Inc.

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