Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM
Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: A subgroup analysis of the DACO-016 trial.
Myelodysplastic syndromes (MDS) are stem cell disorders caused by various gene abnormalities. We performed targeted deep sequencing in 39 patients with high-risk MDS and secondary acute myeloid leukemia (sAML) at diagnosis and follow-up (response and/or relapse), with the aim to define their mutational status, to establish if specific mutations are biomarkers of response to 5-azacytidine (AZA) and/or may have impact on survival. Overall, 95% of patients harbored at least one mutation.
Epigenome-wide analysis reveals specific DNA hypermethylation of T cells during human hematopoietic differentiation.
Epigenomics5 Apr 2018, . Epub 5 Apr 2018
Epigenetic regulation plays an important role in cellular development and differentiation. A detailed map of the DNA methylation dynamics that occur during cell differentiation would contribute to decipher the molecular networks governing cell fate commitment.
Arana P, Paiva B, Cedena MT, Puig N, Cordon L, Vidriales MB, Gutierrez NC, Chiodi F, Burgos L, Anglada LL, Martinez-Lopez J, Hernandez MT, Teruel AI, Gironella M, Echeveste MA, Rosiñol L, Martinez R, Oriol A, De la Rubia J, Orfao A, Blade J, Lahuerta JJ, Mateos MV, San Miguel JF
Prognostic value of antigen expression in multiple myeloma: a PETHEMA/GEM study on 1265 patients enrolled in four consecutive clinical trials.
LeukemiaApr 2018, 32(4)971-978. Epub 3 Nov 2017
Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19
Venous thromboembolism in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with lenalidomide: a systematic review.
Leuk. Lymphoma21 Mar 2018, 1-10. Epub 21 Mar 2018
Lenalidomide has been associated with an increased risk of venous thromboembolism (VTE) in multiple myeloma. It is unclear whether patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are also at such risk. We conducted a systematic review of the incidence of VTE in prospective trials of lenalidomide-treated patients with NHL or CLL. Sixty-eight unique reports were assessed for inclusion. For grade ≥3 VTE, 98 events were reported in 3043 patients (60 studies) (crude incidence: 3.22% [95% confidence interval: 2.6-3.9%]). For any grade VTE, 97 events were reported in 2244 patients (46 studies) (crude incidence: 4.32% [3.5-5.2%]). Subgroup analysis showed no difference based on histological subtype or use of prophylaxis. The study is at risk of bias, largely due to insufficient data from the individual studies. Within the limitations of this systematic review, we found a low risk of VTE in patients with NHL treated with lenalidomide.
Novo CL, Javierre BM, Cairns J, Segonds-Pichon A, Wingett SW, Freire-Pritchett P, Furlan-Magaril M, Schoenfelder S, Fraser P, Rugg-Gunn PJ
Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.
Cell Rep6 Mar 2018, 22(10)2615-2627.
Transcriptional enhancers, including super-enhancers (SEs), form physical interactions with promoters to regulate cell-type-specific gene expression. SEs are characterized by high transcription factor occupancy and large domains of active chromatin, and they are commonly assigned to target promoters using computational predictions. How promoter-SE interactions change upon cell state transitions, and whether transcription factors maintain SE interactions, have not been reported. Here, we used promoter-capture Hi-C to identify promoters that interact with SEs in mouse embryonic stem cells (ESCs). We found that SEs form complex, spatial networks in which individual SEs contact multiple promoters, and a rewiring of promoter-SE interactions occurs between pluripotent states. We also show that long-range promoter-SE interactions are more prevalent in ESCs than in epiblast stem cells (EpiSCs) or Nanog-deficient ESCs. We conclude that SEs form cell-type-specific interaction networks that are partly dependent on core transcription factors, thereby providing insights into the gene regulatory organization of pluripotent cells.