Background
Accumulating evidence suggests that post traumatic stress disorder (PTSD) may accelerate cellular aging and lead to premature morbidity and neurocognitive decline.
Methods
This study evaluated associations between PTSD and DNA methylation (DNAm) age using recently developed algorithms of cellular age by Horvath (2013) and Hannum et al. (2013). These estimates reflect accelerated aging when they exceed chronological age. We also examined if accelerated cellular age manifested in degraded neural integrity, indexed via diffusion tensor imaging.
Results
Among 281 male and female veterans of the conflicts in Iraq and Afghanistan, DNAm age was strongly related to chronological age (rs ~.88). Lifetime PTSD severity was associated with Hannum DNAm age estimates residualized for chronological age (β = .13, p= .032). Advanced DNAm age was associated with reduced integrity in the genu of the corpus callosum (β = −.17, p= .009) and indirectly linked to poorer working memory performance via this region (indirect β = − .05, p= .029). Horvath DNAm age estimates were not associated with PTSD or neural integrity.
Conclusions
Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition.
The ALL-1 gene, located on chromosome band 11q23, is fused to a variety of other genes by reciprocal chromosomal translocations present in 5-10% of human acute leukemias. We have recently reported the detection by Southern blot of ALL-1 gene rearrangements in adult patients with acute myeloid leukemia lacking cytogenetic evidence of 11q23 translocations. These include 2 of 19 patients with normal karyotypes as well as 3 of 4 patients with trisomy 11. To characterize the abnormal ALL-1 genes, we cloned the ALL-1 rearrangements from two patients with trisomy 11. Characterization of the clones, together with Southern blot analysis, indicates that the ALL-1 rearrangement in both patients is the result of a direct tandem duplication of a portion of the ALL-1 gene spanning exons 2-6. The partial ALL-1 duplication is also detected by Southern blot analysis in a patient with a normal karyotype. RNA PCR and DNA sequence analysis show that the partially duplicated ALL-1 gene is transcribed into mRNA capable of encoding a partially duplicated protein. Partial duplication of ALL-1, in which a portion of a putative protooncogene is fused with itself, represents an additional genetic mechanism for leukemogenesis. Our findings suggest that the presence of trisomy in malignancy may sometimes indicate the partial duplication of a cellular protooncogene.
Aim:We examined concordance of methylation levels across the Illumina Infinium HumanMethylation450 BeadChip and the Infinium MethylationEPIC BeadChip.Methods:We computed the correlation for 145 whole blood DNA samples at each of the 422,524 CpG sites measured by both chips.Results:The correlation at some sites was high (up to r = 0.95), but many sites had low correlation (55% had r < 0.20). The low correspondence between 450K and EPIC measured methylation values at many loci was largely due to the low variability in methylation values for the majority of the CpG sites in blood.Conclusion:Filtering out probes based on the observed correlation or low variability may increase reproducibility of BeadChip-based epidemiological studies.
Standard allogeneic stem cell transplant (allo-SCT) regimens have been associated with a high transplant-related mortality (TRM) in multiple myeloma (MM). Nonmyeloablative therapy can establish stable engraftment after allo-SCT and maintain the antitumor effect with less toxicity, which is important in heavily pretreated and elderly patients. We report on 16 poor-risk MM patients receiving allo-SCT from an HLA-matched (n ؍ 14) or mismatched (n ؍ 2) sibling following conditioning with melphalan 100 mg/m 2 (MEL-100). Ten patients had refractory relapse, 4 responsive relapse, and 2 patients were in near complete remission (nCR) with poor-prognosis disease. Patients had received 1 (n ؍ 9) or 2 (n ؍ 7) prior autotransplants. Donor lymphocyte infusions (DLIs) were given to 14 patients with no clinical evidence of graft versus host disease (GVHD) either to attain full donor chimerism (n ؍ 4) or to eradicate residual disease (n ؍ 10). Fifteen patients showed myeloid engraftment, and 12 patients were full donor chimeras at day
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