Learning More About MPN Cell Metabolism to Help Identify Novel Points of MPN Therapy

  • MPNRF | January 16, 2024


    Shannon Elf, PhD,    University of Utah  Huntsman Cancer Institute

    The metabolic landscape of MPNs is an extremely understudied area in the field. Solid tumor treatment has benefited tremendously from studying cellular metabolism in a number of cancers, and Dr. Shannon Elf, a junior investigator at University of Chicago, believes the same can be true for MPNs. 

    MPNRF funded a project led by Dr. Elf through a 2022 Thrive award, Dissecting the pathophysiological role of GLUT1 in driving type 1 CALR-mutated myeloproliferative neoplasms. “This is just one of several projects ongoing in my lab to dissect the unique metabolism of MPN cells in order to identify novel points of therapy.” 

    While still in high school, Dr. Elf was profoundly impacted when a close friend “went so quickly from a healthy, happy teenager to passing away” from acute myeloid leukemia (AML). She became interested in blood cancers, and says she never looked back. “I hope to honor him with the work I am doing.

    About this research Project:

    •  Mutations in calreticulin (CALR) protein represent the second most common genetic abnormality in MPNs, after JAK2.
    •  There are two types of mutations in CALR, Type-1 and Type-2, type 1 mutations are typically associated with a more aggressive disease course.
    • This project looks to understand how these metabolic changes occur, particularly related to up-regulated glucose uptake in mutant cells, and how targeting it can specifically kill typ 1 CALR-mutated MPN cells, while sparing normal ones.  
    • This study is focused on a protein called beta 1 integrin which shows elevated activation on JAK2 mutated stem cells, versus normal cells.
    • The goal of this project is to determine if the therapeutic use of the anti-beta 1 integrin antibody can lead to complete MPN stem cell exhaustion (with potentially curative implications) and be a viable and safe therapy.