Background: DNA is the instruction book that tells a cell when to grow, divide, and develop. In adult cancers, many words in the instruction book are misspelled  resulting in malignancy. While adult cancers are caused by numerous DNA errors, or mutations, that accumulate over a lifetime, pediatric cancers have few mistakes in spelling. How do pediatric cancers arise with such few DNA errors? It turns out that pediatric cancers are caused by misspaced words, not misspelled words.

Background: Chimeric Antigen Receptor (CAR) T cell therapy has been a transformative treatment for children with acute lymphoblastic leukemia (ALL) whose disease has relapsed or not responded to other therapies. However, CAR T-cell therapy is also associated with toxicities, which may be severe. One common side effect is acute kidney injury, but the spectrum of kidney disease has not previously been well described. In addition, we do not know if CAR T- cell therapy has any long-term effects on the kidney.

Background: Acute leukemia is the most common childhood cancer  and remains highly lethal. Even with the best treatments, almost half of children with acute myeloid leukemia (AML) do not survive. Survival rates of pediatric AML have remained distressingly static for the past two decades. A key barrier to improving outcomes in pediatric AML is understanding relapsed disease, which is a major driver of mortality. Certain genetic changes, or mutations, in leukemia cells make them more likely to relapse.

Lay Summary: As we enter into an era of precision pediatric oncology, it is becoming increasingly important to identify the factors that underlie the risk of brain tumor development. This challenge is particularly relevant for individuals with cancer predisposition syndromes like neurofibromatosis type 1 (NF1), where 15-20% of children born with a germline NF1 gene mutation develop optic pathway gliomas (OPGs).

Lay Summary: Diffuse Intrinsic Pontine Gliomas,  (DIPGs), are aggressive and deadly brain tumors that occur in children. These tumors are located in  the brainstem. Currently, there is no treatment for DIPGs, and patients invariably succumb to the disease. To find ways to treat DIPGs, we need to better understand how they arise, and how they become so aggressive.