Farrar and colleagues reveal role of key transcription factor networks in acute lymphoblastic leukemia

Treatment of children with B-cell acute lymphoblastic leukemia (B-ALL), the most common of childhood cancers, has been one of cancer chemotherapy’s success stories, with 80-90 percent of treated patients eclipsing the five-year event free benchmark.  Yet B-ALL remains a leading cause of cancer-related death in children and young adults. A research team led by Michael Farrar, Professor and Utz Chair in Fundamental Immunobiology, investigated transcription factor networks as prognostic markers of disease severity.  They report their findings in “Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival” published in the April 2017 issue of Nature Immunology.

In earlier studies Farrar identified the transcription factor STAT5 as key to the transformation of progenitor B cells into leukemic cells, though the underlying mechanism for transformation was unclear.  In the newly published paper he and colleagues identify regulatory competition between STAT5 and the transcription factors IKAROS and NF-κB.  The STAT5 interaction with the IKAROS - NF-κB network serves as a “molecular switch” governing the proliferation, survival and differentiation of progenitor B cells.  The authors found that high regulatory imbalance between these antagonistic transcription-factor networks serves as a marker for severe disease and poor response to therapy.  They propose that addressing the regulatory imbalance is a potential strategy for inhibiting progenitor B cells from becoming cancerous.

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