Molecules That Drive The Development Of 3 Forms Of Leukemia Point To New Potential Therapeutic Targets

 A team of researchers, lead by Dr. Ari Melnick of Weill Cornell Medical College, have linked epigenetic regulation disruption, or chemical modification of DNA, with the actions of oncogenic proteins involved in acute lymphoblastic leukemia (ALL).

They examined three forms of adult B-acute lymphoblastic leukemia (B-ALL).  All types feature master regulatory gene mutations, which cause cells in the bone marrow to produce cancer-promoting proteins.  The researchers performed DNA methylation and gene expression profiling on 215 patients. 
Among patients with BCR-ABL1-positive B-ALL, they found that the most epigenetically deregulated gene, a CD25 protein-coding gene identified as interleukin-2 receptor alpha, was associated with significantly worse patient outcomes. With this information, CD25 could be used to biomarker to test patients who are at risk for poorer outcomes.  The team also demonstrated, using CD25 antibodies, that leukemic cells expressing the gene could be destroyed.

In patients with E2A-PBX1-positive B-ALL, the researchers found data that suggested the E2A-PBX1 fusion protein directly remodeled the epigenome, or chemical compounds that modify, or control the genome, and caused aggressive symptoms of B-ALL.

The team also found that the epigenetic programming effects of the cancer protein MLLr, in patients with MLLr-B-ALL, caused the activation of a cancer protein called BCL6.  With this information, the researches developed a BCL6 inhibitor, which effectively destroyed the ALL cells in patients involved in the clinical trial.

I found this article interesting because I want to become an oncologist after I graduate.  Many important people in my life have developed cancer, and I personally want to help in some way.  Articles like this that offer both significant insights into a disease and possible treatments, make me feel like I can do the same for people.

Abstract: Integrative Epigenomic Analysis Identifies Biomarkers and Therapeutic Targets in Adult B-Acute Lymphoblastic Leukemia

Article:  Molecules That Drive The Development of 3 Forms of Leukemia Point to New Potential Therapeutic Targets