Welcome!

Agile Computing Authors: Pat Romanski, Shelly Palmer, Glenda Sims, Paul Simmons, APM Blog

News Feed Item

Gene sequencing project identifies abnormal gene that launches rare childhood leukemia

St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project discovery provides insight into a tough-to-cure form of acute myeloid leukemia that lays the groundwork for clinical care advances

MEMPHIS, Tenn., Nov. 12, 2012 /PRNewswire/ -- Research led by the St. Jude Children's Research Hospital – Washington University Pediatric Cancer Genome Project has identified a fusion gene responsible for almost 30 percent of a rare subtype of childhood leukemia with an extremely poor prognosis.

To view the multimedia assets associated with this release, please click: http://www.multivu.com/mnr/58586-st-jude-children-s-research-hospital-gene-sequencing-childhood-leukemia

The finding offers the first evidence of a mistake that gives rise to a significant percentage of acute megakaryoblastic leukemia (AMKL) cases in children. AMKL accounts for about 10 percent of pediatric acute myeloid leukemia (AML). The discovery paves the way for desperately needed treatment advances.

Investigators traced the genetic misstep to the rearrangement of chromosome 16, which brings together pieces of two genes and sets the stage for production of an abnormal protein. The fusion protein features the front end of CBFA2T3, a blood protein, and the back of GLIS2, a protein that is normally produced only in the kidney. Work that appears in the November 13 edition of the journal Cancer Cell reports that in a variety of laboratory models the CBFA2T3-GLIS2 protein switched on genes that drive immature blood cells to keep dividing long after normal cells had died. This alteration directly contributes to leukemia.

AMKL patients with the fusion gene were also found to be at high risk of failing therapy. Researchers checked long-term survival of 40 AMKL patients treated at multiple medical centers around the world and found about 28 percent of patients with the fusion gene became long-term survivors, compared to 42 percent for patients without CBFA2T3-GLIS2. Overall long-term survival for pediatric AML patients in the U.S. is now 71 percent.

"The discovery of the CBFA2T3-GLIS2 fusion gene in a subset of patients with AMKL paves the way for improved diagnostic testing, better risk stratification to help guide treatment and more effective therapeutic interventions for this aggressive childhood cancer," said James Downing, M.D., St. Jude scientific director and the paper's corresponding author. The first author is Tanja Gruber, M.D., Ph.D., an assistant member in the St. Jude Department of Oncology.

Co-author Richard Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis, noted: "We identified this unusual gene fusion by comparing the genome of children's healthy cells with the genome of their cancer cells. This type of in-depth exploration and analysis is crucial to finding unexpected structural rearrangements in the DNA that can lead to cancer. With this discovery, we now can search for more effective treatment options that target this precise defect."

The study is part of the Pediatric Cancer Genome Project, a three-year collaboration between St. Jude and Washington University to sequence the complete normal and cancer genomes of 600 children and adolescents with some of the most aggressive and least understood cancers. The human genome is the instruction book for assembling and sustaining a person. The instructions are packaged in the DNA molecule. Sequencing the genome involves determining the exact order of the four chemical bases that make up DNA. Human DNA is organized into 46 chromosomes.

"We focused on AMKL because no one had any idea of what caused this leukemia in most patients," Gruber said. The study excluded AMKL patients who were infants or children with Down syndrome because earlier research had linked their disease to other chromosomal rearrangements.

When researchers in this study sequenced just the genes that were switched on in the AMKL cells of 14 young patients, the scientists discovered half carried the CBFA2T3-GLIS2 fusion. Additional fusion genes were identified in five of the other patients. Each of those fusion genes occurred in a single patient. The genes involved included HOXA9 and MN1, both previously linked to leukemia, and GATA2 and FLII, which play roles in normal development of the megakaryocytic blood cells that are targeted in AMKL. Megakaryocytes produce the platelets that help blood clot.

Additional sequencing of DNA from adult and pediatric AMKL patients, including whole genome sequencing of the normal and cancer cells of four young AMKL patients, found the CBFA2T3-GLIS2 protein was unique to pediatric AMKL. Of the 48 pediatric AMKL patients screened in this study, 13 carried the fusion gene. None of 28 adult AMKL patients screened had the gene.

"Whole genome sequencing has allowed us to detect alterations in cancer cells that were previously unknown. Many of these changes contribute directly to the development of cancer," Gruber said. "Such sequencing also provides the deeper understanding of the disease that is critical for developing more effective, less-toxic targeted therapies."

GLIS2 is a transcription factor, meaning it attaches to DNA and turns genes on or off. GLIS2 is normally switched off in blood cells and has not been previously linked to cancer.

Working in several laboratory models, researchers showed that GLIS2, either alone or in the fusion gene, increased the activity of other genes in pathways that control cell functions disrupted in cancer. The genes include BMP2 and BMP4, which are now the focus of additional research. The genes are in a pathway that is active early in the developing blood system. This study implicated the genes in AMKL.

The study's other authors are Amanda Larson Gedman, Jinghui Zhang, Cary Koss, Suresh Marada, Shann-Ching Chen, Stacey Ogden, Jinjun Dang, Gang Wu, Stanley Pounds, Lei Shi, John Easton, Heather Mulder, Michael Rusch, Matthew Parker, Jing Ma, Sheila Shurtleff, Jeffrey Rubnitz and Ching-Hon Pui, all of St. Jude;  Huy Ta, Vedant Gupta, Anna Andersson, Michael Barbato, Jayanthi Manne, Jianmin Wang, Ramapriya Ganti and Ina Radtke, all formerly of St. Jude; Xiaoping Su, Steven Kornblau, Farhad Ravandi and Hagop Kantarjian, all of  MD Anderson Cancer Center, Houston; Swati Ranade, Pacific Biosciences, Menlo Park, Calif.; Li Ding, Timothy Ley and Elaine Mardis, all of Washington University; Giovanni Cazzaniga and Andrea Biondi, both of University of Milan-Bicocca, Monza, Italy; Stephen Nimer, Sloan-Kettering Institute, New York; Konstanze Dohner and Hartmut Dohner, both of University of Ulm, Germany; Paola Ballerini, Hospital Armand-Trousseau, Paris;  Daisuke Tomizawa, Tokyo Medical and Dental University; Souichi Adachi, Kyoto University, Japan; Yasuhide Hayashi, Gunma Children's Medical Center, Japan; Akio Tawa, Osaka National Hospital, Japan; Lee-Yung Shih, Chang Gung University, Taipei; and Der-Cherng Liang, Mackay Memorial Hospital, Taipei.

The research was funded in part by the Pediatric Cancer Genome Project, including Kay Jewelers, a lead project sponsor; the National Institutes of Health (P30CA021765); the Eric Trump Foundation; a Leukemia & Lymphoma Society Specialized Center of Research grant and ALSAC.

St. Jude Children's Research Hospital
Since opening 50 years ago, St. Jude Children's Research Hospital has played a pivotal role in pushing overall U.S. pediatric cancer survival rates from 20 to 80 percent. Founded by the late entertainer Danny Thomas, St. Jude is the first and only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. St. Jude is also a leader in research and treatment of life-threatening blood disorders and infectious diseases in children. No family ever pays St. Jude for the care their child receives. To learn more, visit www.stjude.org. Follow us on Twitter @StJudeResearch.

Washington University School of Medicine
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

SOURCE St. Jude Children's Research Hospital

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

@ThingsExpo Stories
DX World EXPO, LLC, a Lighthouse Point, Florida-based startup trade show producer and the creator of "DXWorldEXPO® - Digital Transformation Conference & Expo" has announced its executive management team. The team is headed by Levent Selamoglu, who has been named CEO. "Now is the time for a truly global DX event, to bring together the leading minds from the technology world in a conversation about Digital Transformation," he said in making the announcement.
"Space Monkey by Vivent Smart Home is a product that is a distributed cloud-based edge storage network. Vivent Smart Home, our parent company, is a smart home provider that places a lot of hard drives across homes in North America," explained JT Olds, Director of Engineering, and Brandon Crowfeather, Product Manager, at Vivint Smart Home, in this SYS-CON.tv interview at @ThingsExpo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
SYS-CON Events announced today that Conference Guru has been named “Media Sponsor” of the 22nd International Cloud Expo, which will take place on June 5-7, 2018, at the Javits Center in New York, NY. A valuable conference experience generates new contacts, sales leads, potential strategic partners and potential investors; helps gather competitive intelligence and even provides inspiration for new products and services. Conference Guru works with conference organizers to pass great deals to gre...
The Internet of Things will challenge the status quo of how IT and development organizations operate. Or will it? Certainly the fog layer of IoT requires special insights about data ontology, security and transactional integrity. But the developmental challenges are the same: People, Process and Platform. In his session at @ThingsExpo, Craig Sproule, CEO of Metavine, demonstrated how to move beyond today's coding paradigm and shared the must-have mindsets for removing complexity from the develop...
In his Opening Keynote at 21st Cloud Expo, John Considine, General Manager of IBM Cloud Infrastructure, led attendees through the exciting evolution of the cloud. He looked at this major disruption from the perspective of technology, business models, and what this means for enterprises of all sizes. John Considine is General Manager of Cloud Infrastructure Services at IBM. In that role he is responsible for leading IBM’s public cloud infrastructure including strategy, development, and offering m...
"Evatronix provides design services to companies that need to integrate the IoT technology in their products but they don't necessarily have the expertise, knowledge and design team to do so," explained Adam Morawiec, VP of Business Development at Evatronix, in this SYS-CON.tv interview at @ThingsExpo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
To get the most out of their data, successful companies are not focusing on queries and data lakes, they are actively integrating analytics into their operations with a data-first application development approach. Real-time adjustments to improve revenues, reduce costs, or mitigate risk rely on applications that minimize latency on a variety of data sources. In his session at @BigDataExpo, Jack Norris, Senior Vice President, Data and Applications at MapR Technologies, reviewed best practices to ...
Widespread fragmentation is stalling the growth of the IIoT and making it difficult for partners to work together. The number of software platforms, apps, hardware and connectivity standards is creating paralysis among businesses that are afraid of being locked into a solution. EdgeX Foundry is unifying the community around a common IoT edge framework and an ecosystem of interoperable components.
Large industrial manufacturing organizations are adopting the agile principles of cloud software companies. The industrial manufacturing development process has not scaled over time. Now that design CAD teams are geographically distributed, centralizing their work is key. With large multi-gigabyte projects, outdated tools have stifled industrial team agility, time-to-market milestones, and impacted P&L stakeholders.
"Akvelon is a software development company and we also provide consultancy services to folks who are looking to scale or accelerate their engineering roadmaps," explained Jeremiah Mothersell, Marketing Manager at Akvelon, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
"IBM is really all in on blockchain. We take a look at sort of the history of blockchain ledger technologies. It started out with bitcoin, Ethereum, and IBM evaluated these particular blockchain technologies and found they were anonymous and permissionless and that many companies were looking for permissioned blockchain," stated René Bostic, Technical VP of the IBM Cloud Unit in North America, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Conventi...
In his session at 21st Cloud Expo, Carl J. Levine, Senior Technical Evangelist for NS1, will objectively discuss how DNS is used to solve Digital Transformation challenges in large SaaS applications, CDNs, AdTech platforms, and other demanding use cases. Carl J. Levine is the Senior Technical Evangelist for NS1. A veteran of the Internet Infrastructure space, he has over a decade of experience with startups, networking protocols and Internet infrastructure, combined with the unique ability to it...
22nd International Cloud Expo, taking place June 5-7, 2018, at the Javits Center in New York City, NY, and co-located with the 1st DXWorld Expo will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud ...
"Cloud Academy is an enterprise training platform for the cloud, specifically public clouds. We offer guided learning experiences on AWS, Azure, Google Cloud and all the surrounding methodologies and technologies that you need to know and your teams need to know in order to leverage the full benefits of the cloud," explained Alex Brower, VP of Marketing at Cloud Academy, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clar...
Gemini is Yahoo’s native and search advertising platform. To ensure the quality of a complex distributed system that spans multiple products and components and across various desktop websites and mobile app and web experiences – both Yahoo owned and operated and third-party syndication (supply), with complex interaction with more than a billion users and numerous advertisers globally (demand) – it becomes imperative to automate a set of end-to-end tests 24x7 to detect bugs and regression. In th...
"MobiDev is a software development company and we do complex, custom software development for everybody from entrepreneurs to large enterprises," explained Alan Winters, U.S. Head of Business Development at MobiDev, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
Coca-Cola’s Google powered digital signage system lays the groundwork for a more valuable connection between Coke and its customers. Digital signs pair software with high-resolution displays so that a message can be changed instantly based on what the operator wants to communicate or sell. In their Day 3 Keynote at 21st Cloud Expo, Greg Chambers, Global Group Director, Digital Innovation, Coca-Cola, and Vidya Nagarajan, a Senior Product Manager at Google, discussed how from store operations and ...
"There's plenty of bandwidth out there but it's never in the right place. So what Cedexis does is uses data to work out the best pathways to get data from the origin to the person who wants to get it," explained Simon Jones, Evangelist and Head of Marketing at Cedexis, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
SYS-CON Events announced today that CrowdReviews.com has been named “Media Sponsor” of SYS-CON's 22nd International Cloud Expo, which will take place on June 5–7, 2018, at the Javits Center in New York City, NY. CrowdReviews.com is a transparent online platform for determining which products and services are the best based on the opinion of the crowd. The crowd consists of Internet users that have experienced products and services first-hand and have an interest in letting other potential buye...
SYS-CON Events announced today that Telecom Reseller has been named “Media Sponsor” of SYS-CON's 22nd International Cloud Expo, which will take place on June 5-7, 2018, at the Javits Center in New York, NY. Telecom Reseller reports on Unified Communications, UCaaS, BPaaS for enterprise and SMBs. They report extensively on both customer premises based solutions such as IP-PBX as well as cloud based and hosted platforms.