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The Johns Hopkins University School of Medicine

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The Johns Hopkins University School of Medicine
The Johns Hopkins University School of Medicine
The Johns Hopkins University School of Medicine

Certain visible changes in the chromosomes and mutations in the genes correlate with good or bad prognosis in leukemia. FLT3 is one of the most frequently mutated genes in pediatric AML and also plays an important role in Infant ALL. In both types of pediatric leukemias the FLT3 protein acts as a gas pedal that is permanently pressed to the floor, telling cells to grow out of control. In order to send this signal, FLT3 needs to bind to an energy molecule called ATP.

The Johns Hopkins University School of Medicine

Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia and the leading cause of death in children with cancer. While therapy is often curative, ~10% of children will relapse with recurrent disease and abysmal outcomes. Unfortunately, recent efforts to increase the dose or frequency of standard therapy have failed to prevent relapse. Thus, we have reached the ceiling of efficacy for current therapy and new strategies are needed. Here, we take a novel approach by focusing on HMGA1 proteins as drivers of relapse in leukemia.

Osteosarcoma is a type of bone cancer that begins in bone-forming cells. The conventional treatment strategy involves tumor resection and chemotherapeutic drugs. The 5-year survival rate is about 70% in patients with confined osteosarcoma; however, this regimen largely fails in patients with recurrence and/or when it spreads to other body parts. The prognosis for patients with metastatic disease is grim with an overall 5-year survival rate <20%.

The Johns Hopkins University School of Medicine

 

Pediatric atypical teratoid/rhaboid tumors (ATRT) are among the most deadly malignant pediatric brain cancers. The hallmark of these cancers is mutation or deletion of the SNF5/INI1 gene, which can turn on or off many other genes. We have recently identified the stem cell factor LIN28A, also a regulator of many other genes, as being highly expressed in ATRT. This proposal will investigate the role of master control genes LIN28A and SNF5/INI1 in the development of ATRT.

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