Magic™ Anti-KMT6/EZH2 (Phospho S21) polyclonal antibody

Increasing evidence uncover the essential role of long noncoding RNA (lncRNAs) in bone metabolism and the association of lncRNA with genetic risk of osteoporosis. However, whether lncRNA nuclear paraspeckle assembly transcript 1 (Neat1) is involved remains largely unknown. In the present study, we found that Neat1 is induced by osteoclastic differentiation stimuli. Knockdown of Neat1 attenuates osteoclast formation whereas overexpression of Neat1 accelerates osteoclast formation. In vivo evidence showed that enhanced Neat1 expression stimulates osteoclastogenesis and reduces bone mass in mice. Mechanically, Neat1 competitively binds with microRNA 7 (miR-7) and blocks its function for regulating protein tyrosine kinase 2 (PTK2). Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. We establish for the first time that Neat1 plays an essential role in osteoclast differentiation, and provide genetic mechanism underlying the association of NEAT1 locus with osteoporosis risk. These results enrich the current knowledge of NEAT1 function, and uncover the potential of NEAT1 as a therapeutic target for osteoporosis. (c) 2020 American Society for Bone and Mineral Research.

We validated the use of somatic mutations to determine acute myeloid leukemia (AML) ontogeny in elderly patients. We identified 178 elderly (> 70 years) patients with AML who were divided clinically into primary (n = 95) or secondary (sAML) (n = 82) AML based on prior history of antecedent hematologic disease. Patients were then reclassified into 4 groups based on somatic mutations and cytogenetics as suggested by Lindsley et al. Based on the AML ontogeny proposed, 8 patients were classified as primary AML, 72 patients as sAML, 28 patients had TP53 mutation, and 70 patients were classified as non-otherwise specified. The median overall survival was 22.4, 14, 2.8, and 11.2 months, respectively; 44% of patients (n = 32) classified molecularly as sAML had no prior antecedent hematologic disease. Our data shows that molecular annotation of elderly patients with AML reclassifies a significant proportion of patients as sAML, which may have therapeutic implications. Background: Acute myeloid leukemia (AML) in elderly patients is associated with poor outcomes and often arises from antecedent hematologic disorders (AHD), classified as secondary AML (sAML). Patients and Methods: To validate the use of somatic mutations to determine AML ontogeny in the elderly population, we identified 178 elderly (> 70 years) patients with AML with NexGen Sequencing data. Patients were divided clinically into primary AML (pAML) or sAML based on prior history of AHD. Patients were then reclassified into 4 groups based on somatic mutations and cytogenetics as suggested by Lindsley et al: group 1 (pAML) with CBF rearrangements, 11q23/MLL, and NPM1 mutation (MT); group 2 (sAML) with SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 MT; group 3 with TP53 MT; and group 4 as not otherwise specified (NOS). Results: Based on clinical criteria, 95 patients were classified as pAML and 82 patients as sAML. Based on the AML ontogeny proposed, 8 patients were classified as pAML, 72 patients as sAML, 28 patients had TP53 MT, and 70 patients were classified as NOS. The median overall survival was 22.4,14, 2.8, and 11.2 months, respectively. Clinical versus molecular classification was discordant where 25% (n = 2) of patients classified as pAML by molecular signature had a history of AHD, whereas 44% (n = 32) of patients classified molecularly as sAML had no prior AHD. In the TP53 MT and NOS categories, 37% (n = 28) and 43% (n = 70) of patients had AHD, respectively. Conclusion: Our data shows that molecular annotation of elderly patients with AML reclassifies a significant proportion of patients as sAML, which may have therapeutic implications.