Pelotonia Idea Grant Fuels Acute Myeloid Leukemia Research at The James

Rosa Lapalombella

Improving the treatment options for one type of cancer is a launching point, not the finish line for researchers at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James).

John Byrd, MD, Director of the Division of Hematology, and his team at the OSUCCC – James successfully developed a drug called Ibrutinib for the treatment of chronic lymphocytic leukemia (CLL). This daily pill sends chronic lymphocytic leukemia into remission and keeps it there in the vast majority of cases. “It allows people to live with it,” Dr. Byrd said. “It converts it to a chronic illness, like high blood pressure, that you take a pill for every day.”

But this wasn’t enough.

“Dr. Byrd presented us with a new challenge,” said Rosa Lapalombella, PhD, an assistant professor in the Division of Hematology.

The challenge was to “move our knowledge of molecular therapeutics and molecular biology to another cancer,” she said.

Lapalombella accepted the challenge, and with funding from a Pelotonia Idea Grant, she has targeted acute myeloid leukemia (AML), a complex form of blood cancer. AML, and other forms of leukemia, begin in the bone marrow, with leukemia stem cells — or leukemia-initiating cells (LIC) — that multiply and spread throughout the body. Even if the AML is successfully treated, the stem cells remain and will eventually create more leukemia cells.

“Let’s use our expertise on the molecular level to come up with the Ibrutinib for AML,” Lapalombella said of her goal.

Cells need energy to grow, and normal cells have several energy pathways, she explained. But AML cells have been found to be dependent on one primary source of energy: nicotinamide phosphoribosyltransferase (NAMPT). The AML cells utilize NAMPT to produce Nicotinamide adenine dinucleotide (NAD+), which in turn allows them to multiply.

“If you develop a small molecule that depletes NAMPT, now the cancer cells have nothing to make NAD+ and grow,” Lapalombella said, adding that the healthy, non-cancerous cells have several alternative energy pathways and can still thrive without NAMPT.

Karyopharm, a German-based pharmaceutical company with U.S. corporate headquarters in Newton, Mass., has developed a molecule, KPT-9274, that depletes NAMPT. Lapalombella and her team are working with Karyopharm to  develop this new form of treatment for AML.

The Pelotonia Idea Grant will allow Lapalombella and her team to take their research a step further, and target the leukemia-initiating cells (LIC) in bone marrow.

“These leukemia stem cells are very hard to get rid of,” Lapalombella said. “They have a high potential to regenerate and are protected in the bone marrow. Our research will identify if this drug has the property to destroy leukemia initiating cells so that they never come back.”

If all the research and pre-clinical trials are successful, the goal is to submit a proposal to the National Institutes of Health (NIH) “to convince them to fund our clinical trials that would be led by Dr. Byrd,” Lapalombella said.

Lapalombella was born and educated in Italy. She came to the United States, and Ohio State, in 2006, with her husband, Lapo Alinari, MD, PhD, who works in the Department of Internal Medicine at the OSUCCC – James.

Lapalombella played a small role in the development of Ibrutinib. In the past few years, she has worked with Byrd on the development of Selinexor, a drug that works with Ibrutinib.

“Ibrutinib targets the function of BTK in cancer cells; Selinexor targets its presence,” Lapalombella said, adding there is an ongoing clinical trial of this new drug that is funded by the NIH.

The work of a cancer researcher is fraught with ups and downs, frustrations — and sometimes, success.

“Not everything you do works,” Lapalombella said. “But the idea that you can make a difference is so rewarding and makes you want to get back in the lab and do it over and over again.”

Read more about Ibrutinib on our website.