The Influence Of Cd44/ha Signaling On Cml Survival And Resistance To Tyrosine Kinase Inhibitor Treatment
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Author
Humphries, Kylie
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The Influence Of Cd44/ha Signaling On Cml Survival And Resistance To Tyrosine Kinase Inhibitor TreatmentAbstract
The development of tyrosine kinase inhibitors (TKIs) such as imatinib has greatly improved the prognosis and survival of patients diagnosed with chronic myeloid leukemia (CML). However, many CML patients relapse due to the presence of minimal residual disease and the development of TKI resistance. It is unknown exactly what causes the relapse, but based on research from our laboratory we hypothesize that hyaluronic acid produced by fibroblasts in the microenvironment of the bone marrow provides for a protective environment preventing the tumor cells from therapy-induced cell death or senescence. The purpose of this study was to determine the influence of hyaluronic acid and interactions with its receptor (CD44) on CML survival and resistance development. Initially, we examined the effect that stromal cell derived and/or exogenously added HA had on CML resistance to imatinib. Cell survival, apoptosis, CD44 isoform expression, HA production and signaling events elicited by the interactions of HA with specific CD44 isoforms were examined. Furthermore, we examined the potential therapeutic use of compounds known to alter HA production and/or signaling for the treatment of CML.Collections