Research Highlights

Overall Research Goals

  • Advance novel leukemia therapeutics from the lab to the clinic.
  • Develop precision-medicine treatment platforms for specific leukemia subtypes.
  • Dissect the biology and vulnerabilities of leukemic stem cells to understand and eradicate disease recurrence. 
  • Target the bone marrow  niche to eradicate leukemia and prevent relapse.

Research highlights 

  • Enhanced subtype profiling: While leukemia is typically classified as one of four major groups, it is actually a collection of over a hundred abnormalities that lead to uncontrolled cell growth. Our researchers are actively studying the key biological pathways of these subtypes and whether they have specific genetic or molecular targets to focus therapy on.
  • New therapies for relapsed/refractory disease for patients who have undergone and failed standard treatments. These clinical trials may include novel agents developed at City of Hope, or new combinations or regimens of already-approved therapies that may be more effective. Example: The laboratory of Guido Marcucci, M.D., in collaboration with Anthony Stein, M.D., Steven T. Rosen, M.D., and Ya-Huei Kuo, Ph.D., has demonstrated the biological and preclinical relevance of targeting micro RNA miR-126 in acute myeloid leukemia (AML). They have demonstrated the feasibility of miR-126 knock-down in vivo, utilizing a novel, cutting-edge antibody-conjugated nanoparticle approach (NP-antagomiR-126) that disrupts LSC self-renewal. This work is published (Dorrance, Leukemia, 2015) and is currently supported by an NCI R01CA102031. Marcucci and colleagues are currently investigating pharmacokinetic/ pharmacodynamic modeling to define the optimal dose and schedule of NP-antagomiR-126 to be used in vivo.
  • Investigating "leukemia stem cells" that allow the disease to relapse and grow following cancer treatment. By better understanding the biology and weaknesses of these cancer stem cells, scientists and clinicians can develop better treatments that produce lasting cures. Example: SIRT1 Inhibition of CML and AML stem cells (Drs. Li, Kuo, Marcucci and Chen): The research of Ling Li, Ph.D., focuses on inhibition of leukemic stem cells in chronic myelogenous leukemia (CML) and in acute myeloid leukemia (AML). In a project started as a postdoctoral fellow in the lab of Ravi Bhatia, M.D., at City of Hope, Dr Li elucidated the relationship between SIRT1 deacetylase and p53 in CML (Li, Cancer Cell, 2012). He then elucidated the role of SIRT1 in the c-MYC oncogenic pathway and its promotion of drug resistance in FLT3-ITD AML (Li, Cell Stem Cell, 2014). This work was the basis of Dr. Li’s pathway to independence K99/R00 award from the NCI (CA184411) and his recruitment as an assistant professor at City of Hope.