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.