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Genetic and Proteomic Advances Pave the Way for Next-Generation Leukemia Therapies
Date:12/10/2011

ALL remains a leading cause of cancer death in young patients. There are multiple subtypes of ALL with different genetic abnormalities that influence disease outcome and response to therapy, but most current treatments affect all dividing cells, so new targeted therapies that might be effective against non-dividing cells may be required to improve the outcome of this disease.

With the introduction of novel genomic sequencing technologies, researchers can now identify genetic alterations including mutations, chromosomal rearrangements, and structural variations that drive the initiation and progression of leukemia and, importantly, may provide new targets for the development of novel therapies. Prior research had identified a new subtype of B-cell ALL with poor outcome and a gene expression profile similar to that of Philadelphia chromosome (Ph+) ALL (known as Ph-like ALL). Notably, Ph+ ALL is characterized by the expression of BCR-ABL1, which can be effectively treated with tyrosine kinase inhibitors such as imatinib.

To understand the genetic basis underlying Ph-like B-cell ALL, a cooperative research study composed of the Children's Oncology Group, St. Jude Children's Research Hospital, the National Institutes of Health, and British Columbia Genome Sciences Center analyzed the transcriptome (RNA sequence) of 11 Ph-like patients by next-generation sequencing. The team also conducted whole genome sequencing on two of the patients, a process that has become increasingly attractive to understand the full genetic profile of certain types of cancer patients.  

From detailed genetic analysis, new rearrangements, structural changes, and sequence mutations that activate tyrosine kinases and cytokine receptors were identified in 10 of the 11 cases studied. Importantly, these alterations were sensitive to kinase inhibition with existing treatments such as imatinib. The results suggest that the use of genomic sequencing can be used to identify the f
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SOURCE American Society of Hematology
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