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Association details:
| Biomarker: | FLT3-ITD mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Vanflyta (quizartinib) (FLT3 inhibitor) + GMI-1359 (CXCR4 antagonist, E-selectin inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
FLT3 Inhibitors Upregulate CXCR4 and E-Selectin Ligands and CD44 Via ERK Suppression in AML Cells, and Blockade of CXCR4 and E-Selectin Signaling with GMI-1359 Overcomes AML Resistance to Quizartinib in Vitro and In Vivo
Published date:
11/04/2021
Excerpt:
We first checked the effects of FLT3i on the levels of CXCR4 and E-selectin ligands, as well as CD44, in vitro in human MOLM14 AML cells, which harbor FLT3-ITD mutations...The combination of GMI-1359 with quizartinib profoundly reduced leukemia burden and extended survival of the PDX mice compared to the vehicle or the single-agent treatments (median survival was 158 days vs. 82.5, 79 and 128 days, respectively, in combination group vs. vehicle, quizartinib and GMI-1359; p < 0.0001) [Figure 1,2].
DOI:
10.1182/blood-2021-146573
