The research, which was published online in The New England Journal of Medicine, could help base treatments for AML according to the genetic profile of the patient's cancer.
Acute myeloid leukemia, also known as acute myeloblastic leukemia, acute myelogenous leukemia, acute nonlymphocytic leukemia, AML, or ANLL is a malignant disease in which an excess of immature white blood cells accumulate in the blood and bone marrow.
Last year scientists at Albert Einstein College of Medicine of Yeshiva University, published research in the journal Cancer Cell which suggested that targeting elevated HLX (a gene expressed at abnormally high levels in leukemia stem cells in a mouse model of AML) expression may be a promising novel strategy for treating AML.
The study co-leader Timothy Ley, MD, Lewis T. and Rosalind B. Apple Professor of Oncology in the Department of Medicine, both said:
"We now have a genetic playbook for this type of leukemia. We don't know all the rules yet, but we know all the major players. This information can help us begin to understand which patients need more aggressive treatment right up front and which can be treated effectively with standard chemotherapy."
The study, which was funded by the National Institutes of Health (NIH) as part of The Cancer Genome Atlas project, included a total of 200 patients who were all diagnosed with AML.
Another study, soon to be published in the journal Nature and led by Washington University, revealed that adding genomics-based testing to the standard diagnostic workup could help make treatment options more patient specific and better.
In their study, the researchers compared the sequenced DNA of leukemia patients and compared it to the DNA from the patients' other family members. By doing so, they were able to identify the mutations that only occurred in the cancer cells and which contributed to the development of AML.
In addition to sequencing the DNA, the researchers tried to find defects in a chemical cousin of DNA called RNA.
NIH Director Francis S. Collins, MD, PhD, said "These results provide important new insights into the genomics of a deadly and difficult-to-treat cancer, and underscore the power and scope of The Cancer Genome Atlas project."
In comparison to other forms of cancer, AML is only caused by few mutations. There were an average of 13 different mutated genes among AML patients, compared to hundreds which are found in breast cancer tumors.
The scientists believe they have found all of the possible major mutations among patients suffering from AML.
Co-leader Richard K. Wilson, PhD, director of Washington University's Genome Institute and research member of the Siteman Cancer Center, said:
"If only 5 percent of AML cases have a particular gene that is mutated, there is a greater than 99 percent chance that we encountered that mutation at least once in this study. There are still rare mutations that remain to be discovered, but we expect they will fall into the same genetic pathways or gene sets that we identified as being very strongly associated with AML."
David Steensma, MD, at Dana-Farber Cancer Institute and Harvard Medical School in Boston, said: "The use of genomics in the [everyday] practice [of medicine] is just beginning."
In 100 different samples the investigators identified more than 1,800 genes that had mutated at least once, suggesting there are many different routes that lead to AML. However, only 23 of the genes were particularly mutated.
Ley, said:"We didn't realize how few recurrent mutations there were, and no one was thinking even a few years ago that AML was associated with a high frequency of mutations in genes that encode epigenetic modifiers."
Steensma added: "This new information helps narrow the search for likely drug targets and markers that can help predict the severity of AML."
The team grouped the genes into different categories based on their function. The most common form of gene that was found to be mutated were signaling genes and epigenetic modifiers.
Approximately 14,600 people will be diagnosed with AML in the U.S. this year and 10,400 will likely die because of it.
"Anything we can do to improve risk classification in this disease is really important because there is a cure for some patients a stem cell transplant from a matched donor but it is risky and costly and should only be used in patients who need it. For these patients, it's crucial to get the transplant early in the course of the disease."
The findings will allow researchers to determine if mutations can be used to predict prognosis.