Origin of Acute Myeloid Leukemia traced back to Myelodysplastic Syndromes

It has often been seen that patients suffering from myelodyspastic syndromes (MDS) often go on to develop secondary acute myeloid leukemia (AML). However, the genetic reasons behind this progression of MDS into AML were not properly understood until now. A recent study published in the New England Journal of Medicine, has found that AML arises from “founding clones and subclones” of cells that cause MDS.

The research was led by Dr. Timothy Graubert from Washington University in St. Louis. He, along with his colleagues, performed whole genome sequencing of seven paired samples of skin and bone marrow in seven patients who had developed secondary AML. This was done to identify somatic mutations specific to secondary AML. The researchers also genotyped bone marrow samples obtained from each patient in the MDS stage to determine whether the specific somatic mutations were present at that stage. The entire clonal structure of each pair of samples from the MDS to the AML stage was analyzed in order to identify recurrent mutations.

The researchers observed 85% clonality between MDS and AML cells from paired bone marrow samples. An antecedent founding clone was observed in each case and it contained 182 to 660 somatic mutations. A new subclone with hundreds of new mutations was also observed to be emerging from the founding clone. At least one mutation was observed in the coding gene present in all founding clones and subclones.

On the basis of the results observed in the study, the researchers feel that AML evolves from the cells which cause MDS after these cells have undergone multiple cycles of mutations and clonal selection. To treat AML effectively, targeted cancer drugs have to attack the mutations in the founding clone from where the cancer started. Simply targeting the mutations in the cancer cells will not be effective in weeding out the entire cancer from its roots.

Date: 
Monday, March 19, 2012
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