Bone marrow uptake of indolent non-Hodgkin lymphoma on PET/CT with histopathological correlation

postprin

Whole exome sequencing identifies novel mutations in relapsed or refractory acute promyelocytic leukaemia failing treatment with oral arsenic trioxide

Conference abstracts will be published in Haematologica in the near futurepostprin

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.published_or_final_versio

Co-regulation map of the human proteome enables identification of protein functions

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: All mass spectrometry raw files generated in-house have been deposited in the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository36 with the dataset identifier PXD008888. The co-regulation map is hosted on our website at www.proteomeHD.net, and pair-wise co-regulation scores are available through STRING (https://string-db.org). A network of the top 0.5% co-regulated protein pairs can be explored interactively on NDEx (https://doi.org/10.18119/N9N30Q).Code availability: Data analysis was performed in R 3.5.1. R scripts and input files required to reproduce the results of this manuscript are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/ProteomeHD. R scripts related specifically to the benchmarking of the treeClust algorithm using synthetic data are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/treeClust-benchmarking. The R package data.table was used for fast data processing. Figures were prepared using ggplot2, gridExtra, cowplot and viridis.Note that the title of the AAM is different from the published versionThe annotation of protein function is a longstanding challenge of cell biology that suffers from the sheer magnitude of the task. Here we present ProteomeHD, which documents the response of 10,323 human proteins to 294 biological perturbations, measured by isotope-labelling mass spectrometry. We reveal functional associations between human proteins using the treeClust machine learning algorithm, which we show to improve protein co-regulation analysis due to robust selectivity for close linear relationships. Our co-regulation map identifies a functional context for many uncharacterized proteins, including microproteins that are difficult to study with traditional methods. Co-regulation also captures relationships between proteins which do not physically interact or co-localize. For example, co-regulation of the peroxisomal membrane protein PEX11β with mitochondrial respiration factors led us to discover a novel organelle interface between peroxisomes and mitochondria in mammalian cells. The co-regulation map can be explored at www.proteomeHD.net .Biotechnology & Biological Sciences Research Council (BBSRC)European Commissio

Clofarabine

Hosted by the Division of Hematology, Dept of Medicine. the University of Hong KongUpdates of Clofarabine in replased or refractory AML (r/r AML

Ruxolitinib

Hosted by the Division of Hematology, Dept of Medicine. the University of Hong KongRuxolitinib for the management of myelofibrosis (MF), polycythemia vera (PV), and beyon

Polycythemia Vera: Current Management and Emerging Treatment

Patients with polycythemia vera (PV) are at risk of thromboembolic complications, progression to secondary myelofibrosis and rarely transformation to secondary acute myeloid leukemia (AML). The current goal of treatment is to reduce the risk of thromboembolic complications including acute vascular events and venous thromboembolism (VTE). Low-dose aspirin, phlebotomy and cytoreduction are the mainstays in the therapeutic algorithms. However, long-term phlebotomy and cytoreduction with hydroxyurea often impair quality of life, leading to non-compliance and treatment intolerance. They do not modify the natural history of PV and secondary myelofibrosis and leukemia transformation remains to be important causes of treatment failure. Discovery of JAK2 V617F mutation in PV has not only revamped its diagnostic algorithm but provided important grounds for the development of JAK inhibitors. Lestaurtinib was the first reported agent being evaluated in phase II clinical trial. Ruxolitinib was initially approved by the US Food and Drug Administration (FDA) for the treatment of myelofibrosis and recently approved for PV based on Phase II/III study showing its clinical efficacies in improving polycythemia, splenomegaly and PV-related symptoms. Pegylated interferon is generally effective, has tolerable toxicity profile and may potentially modify the natural history of PV