Alex's Lemonade Stand Foundation for Childhood Cancer

Acute myeloid leukemia (AML) is a type of blood cancer that affects around 500 children in the US every year. While many children initially respond well to treatment, unfortunately, over 30 percent experience the cancer coming back, which in many cases is fatal. Recent research has shown that not all leukemia cells are the same. There's a small group of cells within the cancer called leukemia stem cells (LSCs) that are unique and can survive treatment, leading to the cancer returning.

Background

Acute myeloid leukemia (AML) is a genetically complex group of cancers. AML pediatric patients can be divided into those with chromosomal translocations and patients that are cytogenetically normal (CN-AML). Human-in-animal and mouse models of AML have been developed to validate fusion oncoproteins (e.g. AML-ETO and MLL-AF9) as direct effectors of leukemia initiation, disease pathogenesis, and therapeutic response.

Progress in the treatment of children diagnosed with acute myeloid leukemia (AML) has been significant, but hard fought, through intensification of the dosing and timing of therapy and better supportive care for the resulting complications. Despite intensive therapy, often including stem cell transplantation, almost half of the children diagnosed with AML will succumb to refractory or relapsed disease driven by resistant leukemic stem cells (LSC). The resistant LSC lies at the root of failure to achieve remission, and failure to completely eradicate the LSC leads to eventual relapse.

Leukemia is a deadly genetic disease of blood cells. Not all leukemias are the same. Some are more amenable to current treatments, while others are not. The underlying mutations in the DNA of the leukemic cells differentiate both the type of leukemia and the response to current treatment. We have analyzed fruit fly genetics to understand essential developmental signals that underlie the genetic changes found in leukemias that do not currently respond to treatment.