Acute monocytic leukaemia (AML-M5) is a bone marrow disease that affects young children. Astonishingly, the discovery of disease-specific induced pluripotent stem cells (iPSCs) capable of recapitulating human pathogenesis allows us to model this disease in vitro. We had previously generated AML-M5-specific-iPSC (AML-M5-iPSCs) from THP-1 cells obtained from a patient1. These AML-M5-iPSCs were then induced with growth supplements to enter haematopoietic differentiation to generate monocytic cells. We noticed that reprogramming transgenes Oct3/4, Sox2 and c-Myc were unintentionally integrated into the genome of AML-M5-iPSC during reprogramming. Out of scientific interest, the effects of transgene integration on drug responses were investigated. Firstly, the monocytic cells were characterised to determine their morphological and phagocytotic properties, and compared with their parental cell line THP-1 across 5-, 10-, 15-, 20- and 25-day post-differentiation. Subsequently, cytotoxic effect of Doxorubicin at 0.5, 1, 2 and 4μM on both cells were investigated with CCK-SK viability assay, and apoptotic effect investigated with cell cycle analysis. Our results revealed that in terms of size and morphology, both THP-1 and differentiated monocytic cells remained comparable up to 25 days post-differentiation. Within the same duration, their phagocytotic rates also exhibited no significant differences (p>0.05) when investigated with carboxylate-modified red fluorescent latex beads. However, after 24h Doxorubicin treatment, the IC50 value determined for THP-1 cells was 0.59µM, but the IC50 value for differentiated monocytic cells could not be determined; suggesting that they were significantly (p<0.05) less responsive to Doxorubicin. Upon similar treatment conditions, 92.5±3.9% of THP-1 cells entered late apoptosis stage. However, for differentiated monocytic cells, only 0.3±0.2% entered late apoptosis stage, 37.2±1.5% entered necrosis stage and 62.5±1.6% remained in viable stage. Our results showed that transgenes integration was causing monocytic cells to be resistant to Doxorubicin despite the fact the they should only affect haematopoietic differentiation. In addition, the apoptotic effect of Doxorubicin had also been switched to necrotic effect. More interesting, transgene integration did not seem to alter the morphology and phagocytosis of monocytic cells. We postulate that transgenes Oct3/4, Sox2 and c-Myc interfered with the intercalation of Doxorubicin into the DNA, subsequently altering downstream pathways thereby disrupting cell death via apoptosis. In conclusion, further investigations are warranted to determine the mechanism of reprogramming transgene-induced drug resistance in monocytic cells derived from AML-M5-iPSC.