Friday, 25 January 2013

Study proposes a new approach for treating Acute Myeloid Leukemia

Researchers from University of Rochester Medical Centre (URMC) recently reported some great news on Acute Myeoloid Leukemia (AML). Their latest study not only provides new insight on the disease, but also describes how currently available experimental drugs can be effectively used to fight it off.

Most of the current leukaemia treatments are based on the old hypothesis that all leukaemia cells share the same metabolic mechanisms, based on a process known as glycolysis.

The URMC study focuses on the metabolic pathway that leukemia stem cells follow. During their experiments they first found out that the metabolic process of leukemia stem cells is both different and slower compared to the metabolic process that the rest of the leukemia cells follow. According to Eleni Lagadinou, the study's chief researcher, leukemia stem cells generate the required energy via a process, called oxidative phosphorylation.

After their initial revelation,  the researchers continued their study by exploring  the deeper mechanisms of oxidative phosphorylation, in hopes they find a weakness to take advantage of. Their quest was successful as they discovered that the BCL-2 gene plays a crucial role in oxidative phosphorylation. The researchers already knew that various drugs that inhibit the BCL-2 gene are currently under experimentation and decided to test two of them, both of which were already tried on humans.

The drugs were given to patients with Acute Myeoloid Leukemia and worked exactly as expected, they attacked and killed the leukemia stem cells.

According to Lagadinou, a future BCL-2 based treatment has two important advantages. First, unlike today’s conventional treatments it will be more effective against the dormant leukemia stem cells which are the main culprit behind leukemia recurrences. And secondly, at least as the findings suggest, healthy cells aren’t destroyed or harmed by BCL-2 drugs, meaning very few if any adverse effects arising from such a treatment. 

According to Craig T. Jordan, the study's corresponding author, their approach is very unique and can potentially be used for many different types of leukemia. He strongly believes that since the drugs used are already experimented on humans it won't take long for a BCL-2 treatment to arrive.

Acute myeloid leukemia (also known as acute myelogenous leukemia) is a cancer of the myeloid line of blood cells. There are 4 sub-types of AML:
  • Acute myelogenous leukemia
  • Acute lymphoblastic (ALL)
  • Chronic myeloid leukemia (CML)
  • Chronic lymphoblastic (CLL). 

AML is considered to be the most difficult to treat type of leukemia, having a death ratio of about 50 %. More than  50.000 AML cases are diagnosed every year, in the U.S. alone.

Video on Acute Myeloid Leukemia featuring Dr. Frederick Appelbaum 

Lagadinou ED, Sach A, Callahan K, Rossi RM, Neering SJ, Minhajuddin M, Ashton JM, Pei S, Grose V, O'Dwyer KM, Liesveld JL, Brookes PS, Becker MW, & Jordan CT (2013). BCL-2 Inhibition Targets Oxidative Phosphorylation and Selectively Eradicates Quiescent Human Leukemia Stem Cells. Cell stem cell PMID: 23333149

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