A donation of cord blood from a little boy who died of leukemia is leading to key insights into this childhood cancer.

Acute leukemia is the most common cancer in children. There are several subtypes, including acute lymphoblastic leukemia (ALL), which has a high survival rate, and acute megakaryoblastic leukemia (AMKL), which is rare and has a very poor prognosis. Sometimes, leukemias coincide with a genetic mutation known as MLLr – mixed lineage leukemia gene rearrangement – which can make the disease more aggressive and difficult to treat.

American Cancer Society grantee Tanja Gruber, MD, PhD, is investigating what triggers leukemias with the MLL-rearrangement to develop, using a rare donation of cord blood. A California family had contacted her to see if she could use the cord blood from their son, Hendrix Wille, who had AMKL-MLLr.

“They saved his cord blood from birth. Before he died, they went through great lengths and broke through political red tape to make sure that I received his leukemia specimens and cord blood,” says Gruber, an associate member in the division of leukemia/lymphoma at St. Jude Children’s Research Hospital in Memphis. “It’s a precious resource, and I’m very fortunate this family had a desire for this research to happen.”

Genetic Influences of Leukemia

Scientists have long known that the MLLr gene abnormality is present when a child is born. In the early 1990s, London researchers collected small blood samples from newborns, some of whom later developed MLL-rearranged leukemia. Scientists discovered MLLr in the samples, but couldn’t tell which types of cells in the blood carried the mutation.

Gruber separated the cord blood she received into different cell types. She discovered that the MLLr mutation first appeared in stem cells. This type of cell gives rise to other cells with specialized functions, including blood cells. “The fact that the MLLr was present in the cell that gives rise to all blood cells shows that this happens at a very early stage in blood development. Now we need to understand exactly how the leukemia fully developed from that initial hit,” Gruber says.

Gruber’s ACS-funded research aims to discover whether other mutations occurred, and whether they have an effect on the development of leukemia or the leukemia type. Gruber is mapping out genetic changes in leukemia cells to figure out which one, if any, influences MLLr to develop. After that, she plans to introduce different mutations along with MLLr into the bone marrow of mice. “We are trying to see which ones can [lead to] a megakaryoblastic leukemia versus a myeloid leukemia versus a lymphoid,” Gruber says.

The Research Gift

Hendrix Wille and Parents

Doctors diagnosed Hendrix Wille with AMKL shortly after his second birthday. After chemotherapy appeared to successfully tame the aggressive cancer and trigger remission, he received a bone marrow transplant. Four months later, Hendrix relapsed. It was then that doctors discovered he carried the MLLr mutation. Suddenly, the child’s treatment options had become very limited.

“When Hendrix was diagnosed with leukemia, we informed the transplant team that we had saved his [cord blood and] stem cells and asked if they could be used,” says his mother, Roze Wille, a physician. “They said no, that as soon as someone had cancer, the stem cells were thought to be at risk for the same genetic precursors.”

Hendrix died on April 16, 2013. But “his cells are a little piece of him that continue to live on,” says his mother. After being told Hendrix couldn’t benefit from his cord blood, Roze and her husband donated their son’s cord blood and stem cells to Gruber’s research team. “We wanted them to go to someone who would actually use them for something to help other children.”

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