Decoding of a Acute Myeloid Leukemia Genome
Eight New Mutated Genes Are Identified in the AML Cancer progression
Nov 12, 2008
AML (also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute non-lymphocytic leukemia) affects 13000 people per year in the USA alone and 8800 will die from the disease.
AML is a Blood and Bone Marrow Cancer
Acute Myeloid Leukemia (AML) is a cancer of the white blood cells and characterized by a rapid proliferation of abnormal cells. These cancerous cells accumulate in the bone marrow and interfere with the production of normal white or red blood cells.
When cancerous blood cells accumulate in the blood or bone marrow, infection, anemia, or easy bleeding can frequently occur. The leukemia cells can spread outside the blood to other parts of the body, including to organs of the central nervous system such as brain and spinal cord.
New Genes Implicated in AML
A team of American scientists, supervised by Dr Timothy J Ley and Dr Elaine R Mardis from the Washington University School of Medicine (St Louis, USA) has managed to decode the whole genome of a woman patient with AML. The study entitled `DNA sequencing of a cytogenetically normal acute myeloid leukemia genome` has been published on November 6th, 2008 in the famous scientific magazine Nature (2008, vol456, pp66-72).
In this Study, researchers have decoded, or sequenced, the genome of cancerous bone marrow cells as well as the genome from normal skin cells, of the same patient. They did this using a next-generation technique that accelerates the process of gene sequencing. By comparing the normal genome to the genome carried in tumor cells, they found a total of ten genes carrying mutations in the cancerous cells.
From the ten mutated genes, two of them, FLT3 and NPM1, have already been implicated in the process of progression of the AML tumors and are commonly found in AML patients and have been related to a poor prognosis of AML patients.
Genes Involved in Cellular Metabolism May Also be Involved in AML Progression
The other eight mutated genes that were detected in tumor cells have never been reported on in an AML patient genome before, and interestingly enough, have even never been suspected to be involved in AML process. Among these genes, four of them (PTPRT, CDH24, PCLKC and SLC15A1) were associated with other cancers, and the remaining four (KNDC1, GPR123, EBI2 and GRNL1B) are known to be involved in cellular metabolic pathways. Cellular metabolism is an important function that needs to be well controlled to maintain normal cellular function. Deregulation of cellular metabolism is known to be involved in cancer, however, particular proteins or processes, specific to a AML cancer has not yet been thoroughly well understood.
New Therapeutic Avenues for AML Treatment
This research brings two important pieces of information. First, the results highlighted new potential therapeutic targets. However functional assays are needed to confirm the role of these new eight genes in the progression of AML. Second, through this successful result the researchers presented a proof of concept that an approach of whole genome sequencing of tumor cells is a very useful strategy to uncover genes implicated in the disease. This has not been identified by other classical approaches.
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