Navigation Links
Comprehensive Look at Rare Leukemia Finds Relatively Few Genetic Changes Launch Disease

St. Jude scientists identify new genes implicated in childhood acute myeloid leukemia (AML), but analysis underscores the need for more detailed look at the complete AML genome

MEMPHIS, Tenn., July 27 /PRNewswire-USNewswire/ -- The most comprehensive analysis yet of the genome of childhood acute myeloid leukemia (AML) found only a few mistakes in the genetic blueprint, suggesting the cancer arises from just a handful of missteps, according to new findings from St. Jude Children's Research Hospital. The research appears in the July 27 online edition of the Proceedings of the National Academy of Sciences.

"Our data raise the possibility that the development of AML may require fewer genetic alterations than other cancers and that a very limited number of biological processes may need to be altered in hematopoietic stem cells, multi-potential progenitors or committed myeloid progenitors to convert them from a normal cell to AML," the authors noted, referring to several types of immature and maturing cells that give rise to this cancer. James Downing, M.D., St. Jude scientific director and the paper's senior author, said the findings highlight questions about what it takes to transform a normal cell into a cancer cell. "The complement of genetic lesions varies across the different genetic subtypes of AML, but there are very few lesions in total. That is surprising. Most cancers have lots of alterations," he explained.

AML accounts for about 20 percent of childhood leukemia. This year it will be diagnosed in about 500 U.S. children. About 60 percent of young AML patients become long-term survivors.

This study reflects the push to chart the genetic changes that free cells from normal controls and allow the uncontrolled cell division that is a hallmark of cancer. Downing said the findings underscore the need to survey the entire genome of childhood AML and take a more detailed look at particular AML subtypes.

Added Ina Radtke, Ph.D., the paper's lead author: "This rigorous systemic genome-wide study was an important step to direct our future efforts to the most effective strategies to pinpoint lesions in AML." She is a postdoctoral fellow in Downing's laboratory.

For this study, researchers analyzed leukemia cells from 111 St. Jude AML patients representing the seven most common subtypes of the disease. The scientists used several techniques to catalog the changes, including single-nucleotide-polymorphism (SNPs) microarrays to chart genome-wide regions of DNA gain or loss, which are known as copy number alterations (CNAs). To identify point mutations, the researchers also performed DNA re-sequencing of 25 genes that are commonly mutated in adult AML. Point mutations involve a single chemical change in the molecular building blocks of DNA.

The data demonstrated that, in contrast to pediatric acute lymphoblastic leukemia (ALL), AML is characterized by a very low burden of mutations. The researchers found slightly more than two CNAs per AML patient, and less than one point mutation per patient in the genes sequenced. The scientists also reported just 21 percent of AML patients had six or more lesions. By comparison, an earlier St. Jude study reported 77 percent of young ALL patients, a more common cancer, had that much DNA damage. Even more surprising, 34 percent of patients in this study lacked any apparent CNA, and 28 percent of those with a translocation lacked additional DNA abnormalities. Certain chromosomal re-arrangements are known as translocations.

The investigators also found no association between CNAs and patient outcome. Despite the low overall number of lesions in the patients studied, novel recurring regions of genetic alteration were identified that harbor known and potential new cancer genes.

The study also reports cryptic chromosomal translocations in 14 percent of patients in this study who, based on standard testing, appeared to lack such re-arrangements. Cryptic translocations are too small to be detected by conventional testing. Downing said the analysis identified focal CNAs adjacent to genes previously linked to chromosomal translocations. Those genes are MLL, MLLT4, NUP98 and NSD1. These data suggest that chromosomal translocations are more frequent in AML than was previously thought. Identifying the abnormality during diagnostic testing will require additional, more sophisticated screening, Downing said.

Other authors of this paper are Charles Mullighan, Masami Ishii, Xiaoping Su, Jinjun Cheng, Jing Ma, Ramapriya Ganti, Zhongling Cai, Salil Goorha, Stanley Pounds, Xueyuan Cao, Caroline Obert, Jianling Armstrong, Guangchun Song, Raul Ribeiro, Jeffrey Rubnitz, Susana Raimondi and Sheila Shurtleff, all of St. Jude; and Jinghui Zhang, of the Center for Biomedical Informatics and Information Technology, National Cancer Institute.

This work was supported in part by the National Cancer Institute, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit

SOURCE St. Jude Children's Research Hospital
Copyright©2009 PR Newswire.
All rights reserved

Related medicine news :

1. Los Angeles County Launches Its Most Comprehensive Campaign Ever to Encourage HIV Testing
2. Comprehensive VMAT Solution From Elekta on Center Stage at 2009 AAPM Annual Meeting
3. EngagementHealth(R) Launches Comprehensive Wellness Program with Store Kraft - 80% of Employees and Spouses Participate in Programs
4. Global Health Council Welcomes President Obamas Call in Ghana for Comprehensive Global Health Strategy
5. A comprehensive review of addiction to prescription painkillers among patients and physicians
6. NCI Renews Mayo Clinic Cancer Center Support Grant, Extends Comprehensive Status
7. NCI renews Mayo Clinic Cancer Center support grant, extends comprehensive status
8. Lenox Hill Heart and Vascular Institute of New York and Mentice, Inc. Announce the Successful Completion of Their 1st Trans-septal Cardiac Catheterization Training Course: A Comprehensive Hands-On Tutorial with Certification on June 12th and 13th 2009 in
9. Patient Advocates From All 50 States Gather in Nations Capitol to Meet With Lawmakers and Urge Passage of Comprehensive Health Care Reform
10. Former Senate Majority Leaders Baker, Daschle and Dole Release Bipartisan Framework for Comprehensive Health Reform
11. Siemens Makes Innovation Accessible with Comprehensive Molecular Imaging Solutions
Post Your Comments:
(Date:10/13/2015)... ... October 13, 2015 , ... Element Blue ... introduced a new company, RightSensor™ LLC, an Internet of Things (IoT) hardware supplier ... provides a fully-managed approach for customers requiring sensor hardware for critical data environments. ...
(Date:10/13/2015)... ... 13, 2015 , ... Relay (, a technology company that ... significant contract that will provide its award-winning private messaging solution to Independence Blue ... success of its Relay program, IBX Wire™, which now has over 550,000 members ...
(Date:10/13/2015)... ... October 13, 2015 , ... e-con Systems Inc., a leading embedded design ... the industry’s first RGB-IR pixel format camera with a USB 3.0 interface and ... See3CAM family of UVC USB 3.0 cameras, is based on the 1/3-inch OV4682 - ...
(Date:10/13/2015)... Tenn. (PRWEB) , ... October 13, 2015 , ... A ... and that’s why SmileCareClub , the leading remote invisible aligner system, has joined ... who would otherwise go without it. For each aligner treatment plan purchased, SmileCareClub will ...
(Date:10/13/2015)... ... October 13, 2015 , ... Protein is essential to good health. You ... and blood. But how much protein does the average man need in order to ... to the October 2015 issue of Harvard Men's Health Watch . Most Americans ...
Breaking Medicine News(10 mins):
(Date:10/13/2015)... , Oct. 13, 2015   Micell Technologies ... DESSOLVE I and II trials of its MiStent Sirolimus ... ® ) were presented at the 27th Annual ... San Francisco , October 11-15. TCT ... cardiovascular medicine. MiStent SES was designed to optimize vessel ...
(Date:10/13/2015)... -- Health Gorilla ( ) today announced the launch ... secure platform for clinical data and communications poised to change ... healthcare in the US. The launch follows the closing of ... of $4.4M raised to date, with Data Collective ... Harris Barton , Orfin Ventures and ...
(Date:10/13/2015)... 2015 China Jo-Jo Drugstores, Inc. ... "), a leading China-based retail, wholesale and online distributor ... online and retail pharmacies, announced preliminary half year fiscal ... pharmacy through , growing 438% year over ... China Jo-Jo,s online sales are ...
Breaking Medicine Technology: