Welcome!

Agile Computing Authors: Gopala Krishna Behara, Sridhar Chalasani, Tirumala Khandrika, LeanTaaS Blog, Liz McMillan

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
"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.
In his session at 21st Cloud Expo, Raju Shreewastava, founder of Big Data Trunk, provided a fun and simple way to introduce Machine Leaning to anyone and everyone. He solved a machine learning problem and demonstrated an easy way to be able to do machine learning without even coding. Raju Shreewastava is the founder of Big Data Trunk (www.BigDataTrunk.com), a Big Data Training and consulting firm with offices in the United States. He previously led the data warehouse/business intelligence and B...
The 22nd International Cloud Expo | 1st DXWorld Expo has announced that its Call for Papers is open. Cloud Expo | DXWorld Expo, to be held June 5-7, 2018, at the Javits Center in New York, NY, brings together Cloud Computing, Digital Transformation, Big Data, Internet of Things, DevOps, Machine Learning and WebRTC to one location. With cloud computing driving a higher percentage of enterprise IT budgets every year, it becomes increasingly important to plant your flag in this fast-expanding busin...
Nordstrom is transforming the way that they do business and the cloud is the key to enabling speed and hyper personalized customer experiences. In his session at 21st Cloud Expo, Ken Schow, VP of Engineering at Nordstrom, discussed some of the key learnings and common pitfalls of large enterprises moving to the cloud. This includes strategies around choosing a cloud provider(s), architecture, and lessons learned. In addition, he covered some of the best practices for structured team migration an...
Recently, REAN Cloud built a digital concierge for a North Carolina hospital that had observed that most patient call button questions were repetitive. In addition, the paper-based process used to measure patient health metrics was laborious, not in real-time and sometimes error-prone. In their session at 21st Cloud Expo, Sean Finnerty, Executive Director, Practice Lead, Health Care & Life Science at REAN Cloud, and Dr. S.P.T. Krishnan, Principal Architect at REAN Cloud, discussed how they built...
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...
With tough new regulations coming to Europe on data privacy in May 2018, Calligo will explain why in reality the effect is global and transforms how you consider critical data. EU GDPR fundamentally rewrites the rules for cloud, Big Data and IoT. In his session at 21st Cloud Expo, Adam Ryan, Vice President and General Manager EMEA at Calligo, examined the regulations and provided insight on how it affects technology, challenges the established rules and will usher in new levels of diligence arou...
Smart cities have the potential to change our lives at so many levels for citizens: less pollution, reduced parking obstacles, better health, education and more energy savings. Real-time data streaming and the Internet of Things (IoT) possess the power to turn this vision into a reality. However, most organizations today are building their data infrastructure to focus solely on addressing immediate business needs vs. a platform capable of quickly adapting emerging technologies to address future ...
No hype cycles or predictions of a gazillion things here. IoT is here. You get it. You know your business and have great ideas for a business transformation strategy. What comes next? Time to make it happen. In his session at @ThingsExpo, Jay Mason, an Associate Partner of Analytics, IoT & Cybersecurity at M&S Consulting, presented a step-by-step plan to develop your technology implementation strategy. He also discussed the evaluation of communication standards and IoT messaging protocols, data...
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 ...
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 ...
DevOps at Cloud Expo – being held June 5-7, 2018, at the Javits Center in New York, NY – announces that its Call for Papers is open. Born out of proven success in agile development, cloud computing, and process automation, DevOps is a macro trend you cannot afford to miss. From showcase success stories from early adopters and web-scale businesses, DevOps is expanding to organizations of all sizes, including the world's largest enterprises – and delivering real results. Among the proven benefits,...
@DevOpsSummit at Cloud Expo, taking place June 5-7, 2018, at the Javits Center in New York City, NY, is co-located with 22nd Cloud Expo | 1st DXWorld Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait...
Cloud Expo | DXWorld Expo have announced the conference tracks for Cloud Expo 2018. Cloud Expo will be held June 5-7, 2018, at the Javits Center in New York City, and November 6-8, 2018, at the Santa Clara Convention Center, Santa Clara, CA. Digital Transformation (DX) is a major focus with the introduction of DX Expo within the program. Successful transformation requires a laser focus on being data-driven and on using all the tools available that enable transformation if they plan to survive ov...
SYS-CON Events announced today that T-Mobile exhibited at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. As America's Un-carrier, T-Mobile US, Inc., is redefining the way consumers and businesses buy wireless services through leading product and service innovation. The Company's advanced nationwide 4G LTE network delivers outstanding wireless experiences to 67.4 million customers who are unwilling to compromise on qua...
SYS-CON Events announced today that Cedexis will exhibit at SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 - Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Cedexis is the leader in data-driven enterprise global traffic management. Whether optimizing traffic through datacenters, clouds, CDNs, or any combination, Cedexis solutions drive quality and cost-effectiveness. For more information, please visit https://www.cedexis.com.
SYS-CON Events announced today that Google Cloud has been named “Keynote Sponsor” of SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Companies come to Google Cloud to transform their businesses. Google Cloud’s comprehensive portfolio – from infrastructure to apps to devices – helps enterprises innovate faster, scale smarter, stay secure, and do more with data than ever before.
SYS-CON Events announced today that Vivint to exhibit at SYS-CON's 21st Cloud Expo, which will take place on October 31 through November 2nd 2017 at the Santa Clara Convention Center in Santa Clara, California. As a leading smart home technology provider, Vivint offers home security, energy management, home automation, local cloud storage, and high-speed Internet solutions to more than one million customers throughout the United States and Canada. The end result is a smart home solution that sav...
SYS-CON Events announced today that Opsani will exhibit at SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Opsani is the leading provider of deployment automation systems for running and scaling traditional enterprise applications on container infrastructure.
SYS-CON Events announced today that Nirmata will exhibit at SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Nirmata provides a comprehensive platform, for deploying, operating, and optimizing containerized applications across clouds, powered by Kubernetes. Nirmata empowers enterprise DevOps teams by fully automating the complex operations and management of application containers and its underlying ...