000043652 001__ 43652 000043652 005__ 20240822130851.0 000043652 0247_ $$2doi$$a10.6083/bpxhc43652 000043652 037__ $$aIR 000043652 041__ $$aeng 000043652 245__ $$aUsing CRISPR-induced RUNX1 mutations in the HMC-1.2 cell line to study systemic mastocytosis 000043652 260__ $$bOregon Health and Science University 000043652 269__ $$a2024 000043652 336__ $$aAbstract 000043652 520__ $$aSystemic mastocytosis (SM), is a rare blood disorder that is characterized by the over-proliferation of mast cells caused by a gain-of-function mutations in KIT, a receptor tyrosine kinase. The most common mutation in KIT is D816V, which causes ligand-independent activation of the receptor. Inhibitors of KIT-D816V can be highly effective in reducing mast cell proliferation, but some patients develop drug resistance. Drug resistance and poor prognosis of patients with SM is associated with mutations in additional genes such as RUNX1, a transcription factor important for the formation and maturation of blood cells. We hypothesize that RUNX1 mutations may confer resistance to drugs targeting mutant KIT. To test this hypothesis, we used the Lenti-X CRISPR/Cas9 system on a human systemic mastocytosis cell line (HMC-1.2) to introduce a RUNX1 truncating mutation commonly observed in patients with SM. 000043652 540__ $$fCC BY 000043652 542__ $$fIn copyright - joint owners 000043652 650__ $$aMastocytosis$$021866 000043652 650__ $$aMastocytosis, Systemic$$034593 000043652 650__ $$aDrug Resistance, Neoplasm$$031278 000043652 650__ $$aCarcinogenesis$$040251 000043652 650__ $$aMutation$$022555 000043652 6531_ $$aneoplastic human mast cell 000043652 6531_ $$atranscription factor 000043652 6531_ $$aoncogenesis 000043652 6531_ $$atherapeutic resistance 000043652 691__ $$aSchool of Medicine$$041369 000043652 692__ $$aDivision of Oncological Sciences$$041636 000043652 7001_ $$aMercado, Ricardo$$uOregon Health and Science University$$041354 000043652 7001_ $$aCarlson, Hanqian$$uOregon Health and Science University$$041354 000043652 7001_ $$aDarmusey, Lucie$$uOregon Health and Science University$$041354 000043652 7001_ $$aPang, Amara$$uOregon Health and Science University$$041354 000043652 7001_ $$aMaxson, Julia$$uOregon Health and Science University$$041354 000043652 711__ $$aResearch Week$$uOregon Health and Science University$$d2024 000043652 8564_ $$9027c4cee-0d67-44d3-b14f-f403c3ed2d02$$s239104$$uhttps://digitalcollections.ohsu.edu/record/43652/files/ResearchWeek.2024.Mercado.Ricardo.pdf 000043652 980__ $$aResearch Week