Sin Tiong ONG
A haematologist and medical oncologist, Dr. Ong graduated with a medical degree from Cambridge University, and completed his clinical and subspecialty training at Cambridge University, the National University Hospital (Singapore), and the University of Chicago. Prior to returning home to join the Duke-NUS Graduate Medical School, he was on the faculty at the University of California at Irvine, where he directed a research group funded by multiple NIH grants focused on understanding drug-resistance in leukemia. He currently holds Associate Professor appointments in the Cancer & Stem Cell Biology Signature Research Programme at the Duke-NUS Graduate Medical School, and Department of Medicine at Duke University. Dr. Ong continues to see patients, as well as lead research efforts in understanding the mechanisms responsible for drug-resistance in human cancers.
Abstract Title: Identification of BCR-ABL-independent factors which prevent the control of chronic myelogenous leukaemia
Chronic myelogenous leukaemia is a stem cell disorder that is both defined and driven by the oncogenic BCR-ABL kinase. Indeed, the dramatic and profound clinical responses to ABL tyrosine kinase inhibitors (TKI) provide strong evidence for the central role of BCR-ABL in CML pathophysiology. However, a significant proportion of patients, particularly those with late-stage CML or blast crisis (BC), remain refractory to TKIs. Furthermore, the majority of patients with early or chronic phase (CP) CML will continue to require indefinite TKI therapy since the cessation of treatment almost invariably results in disease recurrence. In addition, several East-Asian countries report poorer responses to TKI therapy, which point to the existence of ethnic differences that modulate therapeutic responses. Together, these clinical observations suggest that factors independent of BCR-ABL contribute to various aspects of CML pathophysiology, including the aggressive behaviour of BC CML, disease persistence in CP CML, and drug-resistance. In this talk, we will describe various BCR-ABL-independent factors our group has identified that prevent the long-term control of CML. These include novel pathways that lead to activation of self-renewal programmes in BC CML, microenvironmental factors that contribute to the maintenance of the stem cell phenotype of CML progenitors, and host genetic factors that directly mediate BCR-ABL-independent TKI-resistance. The identification of such factors will suggest novel strategies toward the long-term control of CML, and potentially a cure.
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