Usage Information
Citation Information: JCI Insight. 2016;1(3):e85630. https://doi.org/10.1172/jci.insight.85630.
Abstract
FMS-like tyrosine kinase 3–targeted (FLT3-targeted) therapies have shown initial promise for the treatment of acute myeloid leukemia (AML) expressing FLT3-activating mutations; however, resistance emerges rapidly. Furthermore, limited options exist for the treatment of FLT3-independent AML, demonstrating the need for novel therapies that reduce toxicity and improve survival. MERTK receptor tyrosine kinase is overexpressed in 80% to 90% of AMLs and contributes to leukemogenesis. Here, we describe MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells. In murine orthotopic xenograft models, once-daily oral therapy prolonged survival 2- to 3-fold over that of vehicle-treated controls. Additionally, MRX-2843 retained activity against quizartinib-resistant FLT3-ITD–mutant proteins with clinically relevant alterations at the D835 or F691 loci and prolonged survival in xenograft models of quizartinib-resistant AML. Together, these observations validate MRX-2843 as a translational agent and support its clinical development for the treatment of AML.
Authors
Katherine A. Minson, Catherine C. Smith, Deborah DeRyckere, Clara Libbrecht, Alisa B. Lee-Sherick, Madeline G. Huey, Elisabeth A. Lasater, Gregory D. Kirkpatrick, Michael A. Stashko, Weihe Zhang, Craig T. Jordan, Dmitri Kireev, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Neil P. Shah, Douglas K. Graham
Usage data is cumulative from February 2024 through February 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 554 | 312 |
| 138 | 68 | |
| Figure | 309 | 32 |
| Supplemental data | 48 | 6 |
| Citation downloads | 53 | 0 |
| Totals | 1,102 | 418 |
| Total Views | 1,520 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
