Grant Award Details
This project explores the feasibility of treating acute myeloid leukemia with a combination of 1) 5-Azacytidine chemotherapy, which primes the bone narrow niche and 2) transplantation of autologous HSCs modified to express Vitamin D in the bone marrow niche, thereby promoting terminal differentiation of leukemic stem cells
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Grant Application Details
- Bone Marrow Targeting of Hematopoietic Stem Cells Engineered to Overexpress 25-OH-VD3 1-α-hydroxylase for Acute Myeloid Leukemia Therapy
Research Objective
We propose a new approach to differentiation therapy for acute myeloid leukemia by producing local level of high-dose vitamin D in bone marrow via cell therapy with engineered hematopoietic stem cells
Impact
If proven successful, the proposed research can serve as a major breakthrough in the treatment of multiple subtypes of AML and particularly important for improving survival in older patients.
Major Proposed Activities
- Evaluate homing and expansion of engineered hematopoietic stem cells in bone marrow of human leukemic xenograft (HLX) mice after precondition with 5-Azacytidine
- Optimize the number of injected hematopoietic stem cells without causing hypercalcemia
- Determine if the local concentration of vitamin D3 is sufficient to differentiate leukemic blasts in bone marrow
- Determine the efficacy of combination therapy of 5-Azacytidine and cell therapy by measuring overall survival
- Determine the efficacy of combination therapy of 5-Azacytidine and cell therapy by measuring leukemia burden
- Monitor serum calcium level from peripheral blood during treatment period
Acute myeloid leukemia (AML) has poor outcome, especially in older, ailing patients who can't tolerate aggressive conventional chemotherapy. If proven successful, our work can serve as a major breakthrough in the treatment of multiple subtypes of AML and particularly important for improving survival in older patients. The State of California will be a leading authority in this field. Further, this work will benefit patients around the world, not limited citizens of California