Tag: TET2

Myelodysplastic syndromes (MDS) is a group of clonal hematopoietic neoplasms characterized by the combination of persistent unexplained cytopenia (or cytopenias) and morphologic dysplasia and a propensity to progress to bone marrow failure or acute myeloid leukemia (AML).1 The treatment landscape for MDS is continually progressing and involves a multidisciplinary approach…

Introduction The ETV6::PDGFRB fusion gene is commonly associated with myeloid neoplasms with monocytosis (such as CMML), and with eosinophilia.1 The PDGFRB gene, located on 5q33, encodes PDGFRβ, a type III tyrosine kinase comprising an extracellular domain consisting of five immunoglobulin (Ig)-like domains, a single-transmembrane helix domain, a juxtamembrance domain, and…

Developing an epigenetic screening platform in human T cells Staphylococcus aureus Cas9 (SaCas9) has been extensively used for genome editing in vivo as its compact size (3,159 bp) relative to the conventional Streptococcus pyogenes Cas9 (SpCas9) enables packaging into adeno-associated virus26,27,28. However, SaCas9 has not been widely used for targeted gene…

Key Points Question  Is clonal hematopoiesis of indeterminate potential (CHIP) detected at the time of hematopoietic stem transplant (HCT) associated with increased rates of cardiovascular disease (CVD) among patients with multiple myeloma (MM) following HCT? Finding  In this cohort study of patients with MM undergoing HCT, CHIP was highly prevalent…

Identification of CH cases from WGS in ISL and UKB We used WGS from 45,510 Icelanders and 130,709 British ancestry participants from the UKB17,18. Average sequencing depth was 33× for UKB and 38× for ISL. Participants with prior diagnoses of hematological disorders or grossly abnormal hematology measurements on entry were…

Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening…

In this issue of Blood, Zhou et al reveal the role of KLHL6 inactivation in chemoresistance in diffuse large B-cell lymphoma (DLBCL).1 KLH6 is a cullin-ring ubiquitin type 3 ligase and a central player in the ubiquitin proteasome system, a cellular system that targets proteins for subsequent degradation, thereby limiting their…

The median age of the patients was 55 years (range 13–74). Median time between SOT and PTLD was 95 months (range 2–338). Most patients had stage IV disease (n = 13, 76%) with a median metabolic tumor volume (MTV) of 302 mL (range 5–2070 mL). Lactate dehydrogenase (LDH) levels ranged from 210 to 5068 (Additional file…

In a recent study published in the Nature Cardiovascular Research, researchers used single-cell sequencing methods to examine the cell-intrinsic effects of hematopoietic stem cells with somatic mutations that result in clonal hematopoiesis of indeterminate potential (CHIP), in circulating cells from heart failure patients. Study: Cell-intrinsic effects of clonal hematopoiesis in…

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32. Article  PubMed  Google Scholar  Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. Cancer J Clin. 2020;70(1):7–30. Article  Google Scholar  Thai AA,…

Data acquisition UKB is a large-scale biomedical database and research resource containing genetic, lifestyle and health information from half a million UK participants. UKB has approval from the North West Multicentre Research Ethics Committee (11/NW/0382) and all participants provided written informed consent. The present study has been conducted under approved…

The Myeloid Cancer Panel cfDNA reference standard is a well-characterized cell line-derived control which contains 15 clinically-relevant variants across 14 genes. This cell-free DNA reference material allows labs to perform reliable and cost-effective validations of myeloid cancer liquid biopsy assays. QC pipelines are supported by controls manufactured under ISO:13485 with…

Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th ediition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36(7):1720–48. doi.org/10.1038/s41375-022-01620-2. Article  PubMed  PubMed Central  Google Scholar  Künstner A, Witte HM, Riedl J, Bernard V, Stolting S, Merz H, et…

Austenaa LMI, Barozzi I, Simonatto M, Masella S, Chiara GD, Ghisletti S, Curina A, Wit ED, Bouwman BAM, Pretis SD, Piccolo V, Termanini A, Prosperini E, Pelizzola M, Laat WD, Natoli G (2015) Transcription of mammalian cis-regulatory elements is restrained by actively enforced early termination. Mol Cell 60(3):460–474 Article  CAS …

Elsallab M, Levine BL, Wayne AS, Abou-El-Enein M. CAR T-cell product performance in haematological malignancies before and after marketing authorisation. Lancet Oncol. 2020;21:e104–e16. Article  CAS  PubMed  PubMed Central  Google Scholar  Kersten MJ, Spanjaart AM, Thieblemont C. CD19-directed CAR T-cell therapy in B-cell NHL. Curr Opin Oncol. 2020;32:408–17. Article  CAS  PubMed …

The following is a summary of “Analysis of core mutation and TET2/ASXL1 mutations DNA methylation profile in myelodysplastic syndrome,” published in the June 2023 issue of Hematology by Feng, et al. For a study on myelodysplastic syndromes (MDS), researchers sought to analyze genetic mutations and clinical characteristics and examine their…

Introduction Non-Hodgkin lymphoma is a heterogeneous group of cancers that starts during immune system differentiation.1 Recent reports show that more than 100 different lymphoma types have been identified.2 These lymphomas originate from cells of the immune system such as B cells, T cells, and dendritic cells. B-cell lymphomas are another…

New analyses from IMerge Phase 3 reported higher 24-week transfusion independence (TI) responses for imetelstat-treated patients vs. placebo across key myelodysplastic syndromes (MDS) subgroups and across spectrum of MDS mutations New data and analyses indicated greater variant allele frequency (VAF) reductions for imetelstat-treated patients vs. placebo across multiple genes commonly…

Diffuse large B cell lymphoma (DLBCL) is a B cell neoplasm characterized by high PIM1 expression, which is responsible for poor prognosis. Activation-induced cytidine deaminase (AID) is closely linked to PIM1 hypermutation in DLBCL. Here, we found that the DNA methyltransferase 1 (DNMT1) level decreased with AID depletion in the…

Methylation-based sequencing appears to be a viable risk-assessment tool for myelodysplastic syndromes (MDS), according to a study presented at the 2023 American Society of Clinical Oncology Annual Meeting. “MDS risk stratification is key for [making] optimal treatment decisions. DNA methylation is associated with MDS biology due to frequent somatic mutations…

Cold Spring Harb Mol Case Stud. 2023 Apr; 9(2): a006256. ,1,2 ,1,2 ,1,2 ,2,3 ,4 and 1,2 Mahvish Q. Rahim 1Pediatric Hematology Oncology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA; 2Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA; April Rahrig 1Pediatric Hematology Oncology,…

Imetelstat, a first-in-class telomerase inhibitor, decreased transfusion dependence and increased hemoglobin counts for patients with heavily transfusion dependent, non-del(5q) lower-risk myelodysplastic syndrome (MDS) that is relapsed or refractory to erythropoiesis stimulating agents (ESAs), according to findings from the phase 3 IMerge trial (NCT02598661) presented during the 2023 ASCO Annual Meeting.1…

Statistically significant and clinically meaningful efficacy has been demonstrated with imetelstat, a first-in-class direct and competitive telomerase inhibitor imetelstat, in patients with heavily transfusion dependent, non-del(5q) lower-risk myelodysplastic syndrome (MDS) that is relapsed or refractory to erythropoiesis stimulating agents (ESAs).1 Findings come from the phase 3 IMerge trial (NCT02598661), which…

Treatment with the first-in-class direct and competitive telomerase inhibitor imetelstat resulted in statistically significant and clinically meaningful efficacy in patients with heavily transfusion dependent, non-del(5q) lower-risk myelodysplastic syndrome (MDS) that is relapsed or refractory to erythropoiesis stimulating agents (ESAs),according to findings from the phase 3 IMerge trial (NCT02598661) presented during…

Results from Phase 3 COMMANDS study, selected for ASCO’s official press program,show nearly twice as many patients treated with Reblozyl achieved superior transfusion independence with concurrent hemoglobin increase vs. epoetin alfa, including in clinically relevant subgroups Reblozyl demonstrated a durable response, with nearly 2.5 years median transfusion independence, 1 year…

FOSTER CITY, Calif.–(BUSINESS WIRE)–May 11, 2023– Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced that five abstracts related to imetelstat, a first-in-class telomerase inhibitor, have been accepted at the European Hematology Association (EHA) Annual Meeting taking place from June 8-11, 2023 in Frankfurt, Germany and virtually. The…

Laurenti, E. & Gottgens, B. From haematopoietic stem cells to complex differentiation landscapes. Nature (London) 553, 418–426 (2018). ADS  CAS  PubMed  Google Scholar  Miller, I. J. & Bieker, J. J. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family…

5-Azacytidine pretreatment resensitizes cisplatin-resistant DLBCL cell lines to cisplatin to varying degrees A platinum-based anti-neoplastic agent is an essential component of salvage regimens for aggressive lymphomas, for example, rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) for relapsed/refractory DLBCL and Hodgkin lymphoma [21]. As a single agent in humans, cisplatin is administered…

Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet. 2016;17:487–500. Article  CAS  PubMed  Google Scholar  Boccaletto P, Stefaniak F, Ray A, Cappannini A, Mukherjee S, Purta E, et al. MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res. 2022;50:D231–D235. Article  CAS  PubMed  Google…

Goldberg, A. D., Allis, C. D. & Bernstein, E. Epigenetics: A landscape takes shape. Cell 128, 635–638 (2007). Article  PubMed  Google Scholar  Mohn, F. & Schübeler, D. Genetics and epigenetics: Stability and plasticity during cellular differentiation. Trends Genet. 25, 129–136 (2009). Article  PubMed  Google Scholar  Takahashi, K. et al. Induction…

Fairchild, Lauren, Whalen, Jeanne, D’Aco, Katie, Wu, Jincheng, Gustafson, Ben, Su, Fei, Leary, Rebecca, Campbell, Katie and Balbin, Oscar (2023) Clonal hematopoiesis detection in patients with cancer using cell-free DNA sequencing. Science translational medicine, 15 (689). ISSN 1946-6242 Abstract In the context of cancer, clonal hematopoiesis of indeterminate potential (CHIP)…

Patient selection and data collection This study retrospectively collected 475 patients diagnosed with de novo DLBCL by two experienced pathologists at the CHCAMS and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. A total of 132 patients with MYD88 variations were included for analysis. The inclusion criteria…

OCT4 alone was insufficient to reprogram PBMCs into iMSCs directly Previously, we reported that lentivirally expressed OCT4 could directly reprogram human cord blood CD34+ hematopoietic progenitor cells into iMSCs with very high efficiency11. Therefore, we first tried to convert human PBMCs into iMSCs by overexpressing OCT4 alone using a clinically…

A mechanism linked to a genetic mutation could help identify patients who are at higher risk of developing leukaemia. A new study published in Blood, focuses on a genetic mutation associated with leukaemia. While some individuals with this mutation remain healthy, others develop the disease. The researchers at the USC Stem…

Credit: Pixabay/CC0 Public Domain Why do some people with a genetic mutation associated with leukemia remain healthy, while others with the same mutation develop the blood cancer? In a new study published in Blood, scientists from the USC Stem Cell laboratory of Rong Lu discovered a mechanism that linked a…

 UniProt:P68135 ACTS      0.867 10  UniProt:P07830  4 act9 [extracellular region] (R-DDI-350725-3) act9 [nucleoplasm] (R-DDI-3321990-3) act9 [cytosol] (R-DDI-201861-3) act9 [plasma membrane] (R-DDI-196016-3) 0.683 5  UniProt:P03372 ESR1  8 p-S118-ESR1 [nucleoplasm] (R-HSA-9024210) monoSUMO1-5K-ESR1 [nucleoplasm] (R-HSA-4090302) Me260-PalmS-ESR1 [plasma membrane] (R-HSA-9637788) PalmS-ESR1 [plasma membrane] (R-HSA-9021057) PalmS-ESR1 [cytosol] (R-HSA-9020974) Me260-ESR1 [cytosol] (R-HSA-9632177) ESR1 [nucleoplasm] (R-HSA-446168)…

Background Lymphoma is a group of heterogeneous hematological malignancies, which are classified into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive NHL. DLBCL can be divided into germinal center B-cell-like (GCB) subgroup and non-GCB subgroup according to the origin of cells….

In general, more than half of MDS patients are diagnosed at age 75 years or older, and the incidence rate of MDS in patients under 50 years of age is as low as less than 1 per 100,000)3. The median number of gene mutations in patients with MDS has been found to…

Applications are invited for a temporary post of a Post-doctoral Research Fellow Level 1 or Level 2 within UCD School of Biomolecular and Biomedical Science. The Chromatin Architecture in Cancer laboratory at University College Dublin, led by Dr. Eric Conway, are recruiting a postdoctoral fellow to work on the role…

Gu, T. P. et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477, 606–610 (2011). Article  CAS  Google Scholar  Wossidlo, M. et al. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat. Commun. 2, 241 (2011). Article  Google Scholar  Iqbal, K., Jin, S….

Martincorena, I. et al. Somatic mutant clones colonize the human esophagus with age. Science 362, 911–917 (2018). CAS  PubMed  PubMed Central  Google Scholar  Yizhak, K. et al. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science 364, eaaw0726 (2019). CAS  PubMed  PubMed Central  Google Scholar  Yokoyama, A….

New research has uncovered how genetic mutations hijack the production of blood cells in different periods of life. Scientists at the Wellcome Sanger Institute, the Cambridge Stem Cell Institute, EMBL’s European Bioinformatics Institute (EMBL-EBI) and collaborators show how these changes relate to ageing and the development of age-related diseases, including…