Myeloid malignancies are heterogeneous diseases of abnormal myeloid progenitor cells. Over the past 10 years, we have been collaborating with hematologists and oncologists to study acute (acute myeloid leukemia; AML) and chronic forms (myelodysplastic syndrome; MDS) of these malignancies. The hypothesis is that integrative bioinformatics analyses of high-dimensional genomics profiles and clinical records lead to discovery of novel prognostic markers and therapeutic targets. Specifically, by integrative analyses of mutations, gene expression, and miRNA expression profiles of de novo AML patients, we showcased strategies of biomarker implementations based on different modalities of cancer multi-omics: miRNAs, mRNAs, gene regulations, and pathways. We developed a 3-miRNA prognostication panel to predict responses to standard chemotherapy and overall survival; these were validated in external cohorts (Leukemia 2015). Furthermore, we proposed for the first time and verified a novel mechanism: NPM1 (a frequently mutated gene in AML) gene mutation modulates miRNA−gene regulation that is associated with prognosis (Leukemia 2016). At the pathway level, we further showed the crosstalk among the pathways of Myc, OXPHOS, mTOR, and stemness governs patients’ response to “7 + 3” induction chemotherapy (European Journal of Haematology 2019). Overall, our studies bring biological and clinical insights into prognostic markers and chemoresistance mechanisms.
Besides hematopoietic malignancies, we have established collaborations to study metastatic castration resistant prostate cancer (mCRPC), hepatocellular carcinoma (HCC), and pediatric cancers.