6:10 PM
 | 
Dec 07, 2017
 |  BC Innovations  |  Targets & Mechanisms

Epiphenomena at ASH

Epigenetics and cell therapies are preclinical hotspots at ASH 2017

While it’s no surprise that cell therapy research is dominant in hematology, the emergence of epigenetics as an equally large focus at this year’s ASH meeting is more notable, reinforcing the resurgence of a field that stumbled to capitalize on its early promise.

BioCentury’s survey of the 4,429 abstracts at this year’s meeting of the American Society of Hematology, which takes place Dec. 9-12 in Atlanta, Georgia, identified epigenetics and cell therapies as two of the meeting’s standout themes, each netting over 200 abstracts across a wide range of indications and development stages.

The analysis also found 16 new therapeutic targets and biomarkers, not previously present in BioCentury’s BCIQ database. While the bulk were presented by academic groups, Celgene Corp. was part of a collaboration that identified MAFB as a potential biomarker for multiple myeloma (MM), and diagnostic play NanoString Technologies Inc. was part of a team that showed CSMD3 could serve as a biomarker for primary CNS lymphoma (see “Novel Targets at ASH2017”).

Moreover, BioCentury identified 29 emerging targets mentioned in zero or one abstract at ASH2016 and four or more abstracts at ASH2017 (see “Emerging Targets at ASH2017”). A broader look at the emerging targets showed they fall into 12 mechanistic categories, dominated by immune modulation (see “Pathways Emerging From ASH.” BioCentury Innovations (Dec. 7, 2017)).

Table: Novel targets at ASH 2017

Select new targets in hematology and hematological malignancies presented at the 2017 American Society of Hematology (ASH) meeting. The list includes proteins and genes with proposed therapeutic potential based on preclinical studies, or with proposed biomarker potential based on genetic association studies. Source: ASH Abstracts as of Dec. 5, 2017

TargetIndication(s)DescriptionInstitutions/CompaniesAbstract code
AT-rich interaction domain 5B (ARID5B)Acute lymphoblastic leukemia (ALL)In vitro studies suggest inhibiting ARID5B could help treat T cell-ALL (T-ALL) by disrupting an oncogenic transcriptional control program. Harvard Medical School; National University of Singapore2502
BCL tumor suppressor 7A (BCL7A)Hodgkin's diseaseExome sequencing on 31 tumor samples from Hodgkin's lymphoma patients identified mutations in genes including immunoglobulin λ-like 5 (IGLL5) and BCL7A and histones including HIST1H1B that could serve as markers for the cancer.Washington University School of Medicine in St. Louis2733
Histone cluster 1H1b (HIST1H1B)
Cell division cycle 20 (CDC20)B cell lymphoma; mantle cell lymphoma (MCL)Patient sample and cell culture studies suggest inhibiting CDC20 could help treat diffuse large B cell lymphoma (DLBCL) and MCL.Vrije University Brussels (VUB)2757
Cell division cycle 37 (CDC37)Non-Hodgkin's lymphoma (NHL)Cell culture studies suggest disrupting the interaction between heat shock protein 90 (Hsp90) and its co-chaperone protein CDC37 could help treat anaplastic large cell lymphoma (ALCL).Cleveland Clinic; University of Kansas2758
CUB and Sushi multiple domains 2 (CSMD2)LymphomaTargeted next-generation sequencing identified mutations in 13 genes including CSMD2 and CSMD3 that could serve as biomarkers for primary central nervous system lymphoma.Budapest National Institute of Oncology; Research Center for Molecular Medicine of the Austrian Academy of Sciences; NanoString Technologies Inc. (NASDAQ:NSTG); Semmelweis University; University College London; University of Pécs4009
CUB and Sushi multiple domains 3 (CSMD3)
HECT, UBA and WWE domain containing 1 E3 ubiquitin protein ligase (HUWE1)Multiple myeloma (MM)In MM cells and cell lines, inhibitors of HUWE1 decreased cell growth alone and in co-culture with MM patient bone marrow-derived stromal cells.Dana-Farber Cancer Institute; Queen's University Belfast3077
Immunoglobulin λ-like polypeptide 5 (IGLL5)Chronic lymphocytic leukemia (CLL); B cell lymphoma; NHL; Hodgkin's disease; MMSeveral sequencing studies on human hematologic malignancy samples identified mutations in IGLL5 that could serve as biomarkers for CLL, diffuse large B cell lymphoma (DLBCL), follicular lymphoma, Hodgkin's lymphoma and MM.Various114; 2733; 4363; 4298; 1452; 1457; 1464
Lysine-specific demethylase 7A (KDM7A)MMIn vitro studies showed that expression of KDM3A and KDM7A was higher in human MM cell lines under hypoxic vs. normoxic conditions and high KDM3A had an anti-apoptotic effect on the cells.Akita University Graduate School of Medicine; Kameda Medical Center3061
Methyl CpG binding domain protein 2 (MBD2)Sickle cell disease; thalassemiaCell culture studies suggest inhibiting MBD2 increases fetal hemoglobin levels, which can help counteract low levels of functional hemoglobin in adults, to help treat sickle cell disease and β-thalassemia. Virginia Commonwealth University; University of North Carolina at Chapel Hill; Massey Cancer Center2220
MAF bZIP transcription factor B (MAFB)MMWhole-exome sequencing studies identified mutations in genes including HUWE1 and MAFB that could serve as markers for MM.Celgene Corp. (NASDAQ:CELG); Dana-Farber Cancer Institute; University of Arkansas for Medical Sciences60
Mitogen-activated protein kinase associated protein 1 (MAPKAP1)Acute myelogenous leukemia (AML)Patient sample and cell culture studies suggest inhibiting MAPKAP1 could help treat AML and sensitize AML cells to the CRAF (RAF1) and receptor tyrosine kinase inhibitor Nexavar sorafenib. Karolinska Institute; National University Cancer Institute of Singapore; University of Texas MD Anderson Cancer Center 3964
Signal transducing adaptor family member 1 (STAP1)Chronic myelogenous leukemia (CML)In a mouse model of CML, STAP1 knockout increased survival, and STAP1 or STAP2 knockout decreased the number of leukemic stem cells compared with normal STAP1 or STAP2 expression.Hokkaido University; International University of Health and Welfare; Osaka University1583
Signal transducing adaptor family member 2 (STAP2)
Tetraspanin 14 (TSPAN14;...

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