Downregulate stem cell factors SOX2, OCT4, and KLF4 in HAP1 TROVE2 CRISPR edited cell lines
Abstract
Chronic myeloid leukemia is characterized
by the translocation of parts of
chromosome 9 to chromosome 22 giving
rise to a fusion protein (BCR-ABL).
Treatment of CML involves the use of
tyrosine kinase inhibitor, imatinib that
specifically targets the BCR-ABL fusion
protein. Resistance to imatinib is due to
point mutations on Tyr177 or Ser177 in the
2
kinase domain of BCR-ABL. Other
resistance mechanisms due to leukemic
stem cells (LSC) that overexpress
pluripotent stem cell markers OCT4, SOX2,
KLF4 and c-MYC. This project aimed at
inducing the expression of BCR-ABL in a
HAP1 TROVE2 CRISPR cell line by
knocking down the transcription factors
OCT4, SOX2, MYC and KLF4. It was
hypothesized that depletion of this stem
cell factors will result in an increased
susceptibility of this cell lines to chemically
modified imatinib compared to its
unmodified imatinib which may open a field
for further studies towards antibody-drug
conjugates to specifically target CML.