TY  - GEN
AB  - Systemic 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.
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
AD  - Oregon Health and Science University
AU  - Mercado, Ricardo
AU  - Carlson, Hanqian
AU  - Darmusey, Lucie
AU  - Pang, Amara
AU  - Maxson, Julia
DA  - 2024
DO  - 10.6083/bpxhc43652
DO  - doi
ID  - 43652
KW  - Mastocytosis
KW  - Mastocytosis, Systemic
KW  - Drug Resistance, Neoplasm
KW  - Carcinogenesis
KW  - Mutation
KW  - neoplastic human mast cell
KW  - transcription factor
KW  - oncogenesis
KW  - therapeutic resistance
L1  - https://digitalcollections.ohsu.edu/record/43652/files/ResearchWeek.2024.Mercado.Ricardo.pdf
L2  - https://digitalcollections.ohsu.edu/record/43652/files/ResearchWeek.2024.Mercado.Ricardo.pdf
L4  - https://digitalcollections.ohsu.edu/record/43652/files/ResearchWeek.2024.Mercado.Ricardo.pdf
LA  - eng
LK  - https://digitalcollections.ohsu.edu/record/43652/files/ResearchWeek.2024.Mercado.Ricardo.pdf
N2  - Systemic 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.
PB  - Oregon Health and Science University
PY  - 2024
T1  - Using CRISPR-induced RUNX1 mutations in the HMC-1.2 cell line to study systemic mastocytosis
TI  - Using CRISPR-induced RUNX1 mutations in the HMC-1.2 cell line to study systemic mastocytosis
UR  - https://digitalcollections.ohsu.edu/record/43652/files/ResearchWeek.2024.Mercado.Ricardo.pdf
Y1  - 2024
ER  -