Blood Journal
Leading the way in experimental and clinical research in hematology

Δ12-prostaglandin J3, an omega-3 fatty acid–derived metabolite, selectively ablates leukemia stem cells in mice

  1. Shailaja Hegde1,*,
  2. Naveen Kaushal1,*,
  3. Kodihalli C. Ravindra1,
  4. Christopher Chiaro1,
  5. Kelsey T. Hafer1,
  6. Ujjawal H. Gandhi1,
  7. Jerry T. Thompson1,
  8. John P. van den Heuvel1,
  9. Mary J. Kennett1,
  10. Pamela Hankey1,
  11. Robert F. Paulson1, and
  12. K. Sandeep Prabhu1
  1. 1Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA


Targeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that Δ12-PGJ3, a novel and naturally produced CyPG from the dietary fish-oil ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the development of leukemia in 2 well-studied murine models of leukemia. IP administration of Δ12-PGJ3 to mice infected with Friend erythroleukemia virus or those expressing the chronic myelogenous leukemia oncoprotein BCR-ABL in the hematopoietic stem cell pool completely restored normal hematologic parameters, splenic histology, and enhanced survival. More importantly, Δ12-PGJ3 selectively targeted leukemia stem cells (LSCs) for apoptosis in the spleen and BM. This treatment completely eradicated LSCs in vivo, as demonstrated by the inability of donor cells from treated mice to cause leukemia in secondary transplantations. Given the potency of ω-3 polyunsaturated fatty acid–derived CyPGs and the well-known refractoriness of LSCs to currently used clinical agents, Δ12-PGJ3 may represent a new chemotherapeutic for leukemia that targets LSCs.

  • Submitted November 5, 2010.
  • Accepted September 14, 2011.
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