The Effects of FLT3 Inhibition on FLT3-Mutated Acute Myeloid Leukemia Cells as a Potential Improved Treatment

ac.comp.abstractAcute Myeloid Leukemia (AML) affects nearly 500,000 individuals annually, making it a prominent avenue of study. About 30% of patients express a genetic insertion mutation within the FLT3 receptor (known as FLT3-ITD) responsible for regulating the hematopoietic process of these cells, worsening patient prognosis. Current treatments include tyrosine kinase inhibitors to eliminate the negative effects of this mutation, but they lack specificity for FLT3 and FLT3-ITD. A specific FLT3-ITD inhibitor (known as FLT3-IN-3) has been newly developed and would be an improved treatment option with less broad-spectrum activity. To begin examining FLT3-IN-3 as a treatment option, its half-maximal inhibitory concentration value (IC50) and its ability to cause differentiation and apoptosis in FLT3-ITD-positive AML cancer cells need to be investigated. Three AML cell lines were utilized that ranged in their amount of FLT3-ITD expression: MV4-11 (homozygous for ITD), PL-21 (heterozygous for ITD), and NB-4 (no ITD, control). A hemocytometer was used to assess cell viability at FLT3-IN-3 concentrations between 1 nM and 10 uM. Results revealed an IC50 value of 300 nM. Cells were then treated at 300 nM for five days before being stained with markers to examine FLT3 expression (CD135), differentiation (CD11b), and apoptosis (phosphatidylserine). Stained cells were imaged with a fluorescent microscope on the Cytation 7 machine and analyzed with ImageJ software. Results revealed an increase in FLT3 expression, differentiation, and apoptosis in the MV4-11 cell line, an increase in apoptosis in the PL-21 cell line, and no change in the NB-4 cell line. These results suggest that FLT3-IN-3 could act as an improved treatment option for patients by providing an effective, specific treatment for FLT3-mutated receptors.
ac.comp.awardBiochemistry, 2024en_US
ac.comp.firstreaderKadmiel, Mahita
ac.comp.languageEnglish
ac.comp.permissionformPublic
ac.comp.secondreadersMurphree, Shaun S.
dc.contributor.authorSwanson, Laineeen_US
dc.contributor.departmentBiochemistry
dc.date.accessioned2024-05-09T14:52:36Z
dc.date.available2024-05-09T14:52:36Z
dc.date.issued2024-04-30
dc.description.majorBiochemistry
dc.identifier.urihttps://hdl.handle.net/10456/57791
dc.subjectCancer
dc.subjectAcute Myeloid Leukemia
dc.subjectMutated FLT3
dc.subjectDifferentiation
dc.subjectApoptosis
dc.titleThe Effects of FLT3 Inhibition on FLT3-Mutated Acute Myeloid Leukemia Cells as a Potential Improved Treatment
dc.typeSenior Project Paper
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