Mutation Underlying Acute Lymphoblastic Leukemia

Nature Communications study explains a complex genomic mutation in childhood leukemia.
Mutation Underlying Acute Lymphoblastic Leukemia

The most common form of cancer in children is B-cell acute lymphoblastic leukemia. Research at St. Jude Children's Research Hospital opens up therapeutic avenues for this form of cancer by pinpointing a genomic pattern that promotes tumor formation. 

Chapter 11: Hematology and Oncology in Atlas of Pediatric Emergence Medicine, 3e, describes the physical symptoms of acute lymphoblastic leukemia. One such symptom is a mediastatal mass, as illustrated in Figure 40-1 (below). 

Patients with specifically B-cell acute lymphoblastic leukemia, or B-ALL, commonly have a mutation that “fuses a segment of the IGH gene with part of the oncogene DUX4,” forming DUX4-IGH. When fused with IGH, DUX4 is expressed far more. 

Researchers at St. Jude extensively sequenced that genomic region. Researchers expected DUX4-IGH to be dominantly expressed, but that was surprisingly not so. While an overabundance of DUX4 causes cell death, a lower amount can create an environment conducive to tumor growth. These findings encouraged the researchers to develop a mouse model of this form of leukemia, by regulating their DUX4 levels. 

Chapter 445: Acute Lymphoblastic Leukemia in Rudolph's Pediatrics, 23e, describes other mutations that can be involved in acute lymphoblastic leukemia, including the fusion of ETV6-RUNX1, BCR-ABL1, and TCF3-PBX1. Aside from the origins and symptoms of acute lymphoblastic leukemia, this chapter provides an overview of treatment and the risks of treatment. 

Figure 445-1 (above) marks an increase in the survival rate of patients with acute lymphoblastic leukemia. Progressive research, such as this study, contribute to this increase by seeking to refine treatment for B-ALL. According to Tanja Grueber, M.D., Ph.D., “The potential of DUX4 as a source of oncogenic stress may provide a unique angle for IGH-DUX4 treatment.” 

Learn more by reading the newly-released study in Nature Communications. 


St. Jude Children's Research Hospital report:

“Long-read sequencing unveils IGH-DUX4translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia” Study:

Chapter 11: Hematology and Oncology: Miller ST, Viswanathan K. HEMATOLOGY AND ONCOLOGY. In: Shah BR, Mahajan P, Amodio J, Lucchesi M. eds. Atlas of Pediatric Emergency Medicine, 3e New York, NY: McGraw-Hill; .§ionid=216056966. Accessed June 26, 2019.

Figure 40-1: Stone C, Humphries RL, Drigalla D, Stephan M. CURRENT Diagnosis & Treatment: Pediatric Emergency Medicine; 2014.

Chapter 445: Acute Lymphonoblastic Leukemia: Tasian, Sarah K., and Elizabeth A. Raetz.. "Acute Lymphoblastic Leukemia." Rudolph's Pediatrics, 23e Ed. Mark W. Kline. New York, NY: McGraw-Hill,§ionid=181402347.

Figure 445-1: Kline MW. Rudolph's Pediatrics, 23e; 2018.