Study overturns basic tenet in leukemia biology

Scientists thought they understood the steps leading to acute myeloid leukemia. But one of the basic tenets in that understanding turns out to be unsound, according to researchers at the OHSU Knight Cancer Institute.

Acute myeloid leukemia, or AML, is the most common blood cancer in adults – and one of the most difficult to treat. The new findings explain why promising treatment approaches may have fallen short. And the results could help guide efforts to develop more effective therapies for the cancer.

Myeloid stem cells in the bone marrow are supposed to mature, or differentiate, to become red blood cells, immune system white blood cells, or clot-forming platelets. These blood cells are short-lived and to maintain populations the bone marrow has to make millions of new blood cells per second.

In people with AML, this massive and tightly regulated output of mature blood cells collapses. Immature stem cells multiply rapidly and reach overwhelming numbers in the bone marrow, blood circulation and other organs.

Textbook explanations specify that various genetic alterations seen in AML conspire to block the differentiation of myeloid stem cells at an immature stage, along with increased proliferation of these cells.

But the Oregon Health & Science University researchers showed that differentiation of stem cells is not actually blocked in AML. Instead, they found that just a slight skewing of the fraction of cells that differentiate is enough to cause an overwhelming buildup of immature stem cells, called myeloid blasts. The findings suggest that therapies designed to slightly adjust the differentiation of stem cells could be a way forward.

“Multi-disciplinary approaches, along with technological advancement, will unravel new things, but if you go back to answer old questions you may find different answers,” said first author Anupriya Agarwal, Ph.D. “You may get surprised.” Agarwal is an associate professor in the OHSU School of Medicine. The paper presenting the research was published in Proceedings of the National Academy of Sciences. OHSU News has the full story.