NDLI: Priority Report: Rearrangements and Amplification of IER3 (IEX-1) Represent A Novel And Recurrent Molecular Abnormality In Myelodysplastic Syndromes (MDS)

Content Provider	PubMed Central
Author	Steensma, David P. Neiger, Jessemy D. Porcher, Julie C. Keats, J. Jonathan Leif, Bergsagel P. Dennis, Thomas R. Knudson, Ryan A. Jenkins, Robert B. Rafael, Santana-davila Kumar, Rajiv Ketterling, Rhett P.
Abstract	IER3 (formerly IEX-1) encodes a 27kDa glycoprotein that regulates death receptor-induced apoptosis, interacts with NF-κb pathways, and increases expression rapidly in response to cellular stresses such as irradiation. Animal models, gene expression microarray experiments, and functional studies in cell lines have suggested a potential role for IER3 in oncogenesis, but to date no abnormalities of IER3 at the DNA level have been reported in patients with neoplasia. Here we describe breakpoint cloning of a t(6;9)(p21;q34) translocation from a patient with a myelodysplastic syndrome (MDS), facilitated by conversion technology and array-based comparative genomic hybridization, which revealed a rearrangement translocating the IER3 coding region away from critical flanking/regulatory elements and to a transcript-poor chromosomal region, markedly decreasing expression. Using split-signal and locus-specific FISH probes, we analyzed 204 patients with diverse hematologic malignancies accompanied by clonal chromosome 6p21 abnormalities, and found 8 additional patients with MDS with IER3 rearrangements (translocations or amplification). While FISH studies on 157 additional samples from patients with MDS and a normal-karyotype were unrevealing, and sequencing the IER3 coding and proximal promoter regions of 74 MDS patients disclosed no point mutations, RT-PCR results suggested that dysregulated expression of IER3 is common in MDS (61% >4 fold increase or decrease in expression with decreased expression primarily in early MDS and increased expression primarily in later MDS progressing towards leukemia), consistent with findings in previous microarray experiments. These data support involvement of IER3 in the pathobiology of MDS.
Related Links	http://dx.doi.org/10.1158/0008-5472.can-09-1428
Ending Page	7523
Page Count	6
Starting Page	7518
File Format	PDF
ISSN	00085472
e-ISSN	15387445
Journal	Cancer research
Issue Number	19
Volume Number	69
Language	English
Publisher Date	2009-10-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Comparison and Implications of Mutational Profiles of Myelodysplastic Syndromes, Myeloproliferative Neoplasms, and Myelodysplastic/Myeloproliferative Neoplasms: A Meta-Analysis

Early detection of transformation to BPDCN in a patient with MDS

Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study

New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge

Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study

Prognostic Impact of Platelet-Large Cell Ratio In Myelodysplastic Syndromes

SF3B1 mutations in myelodysplastic syndromes: A potential therapeutic target for modulating the entire disease process

Current State and Challenges in Development of Targeted Therapies in Myelodysplastic Syndromes (MDS)

Priority Report: Rearrangements and Amplification of IER3 (IEX-1) Represent A Novel And Recurrent Molecular Abnormality In Myelodysplastic Syndromes (MDS)

Similar Documents

Comparison and Implications of Mutational Profiles of Myelodysplastic Syndromes, Myeloproliferative Neoplasms, and Myelodysplastic/Myeloproliferative Neoplasms: A Meta-Analysis

Early detection of transformation to BPDCN in a patient with MDS

Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study

New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge

Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study

Prognostic Impact of Platelet-Large Cell Ratio In Myelodysplastic Syndromes

SF3B1 mutations in myelodysplastic syndromes: A potential therapeutic target for modulating the entire disease process

Current State and Challenges in Development of Targeted Therapies in Myelodysplastic Syndromes (MDS)

Priority Report: Rearrangements and Amplification of IER3 (IEX-1) Represent A Novel And Recurrent Molecular Abnormality In Myelodysplastic Syndromes (MDS)