Targeting circular PCMTD1 in leukemias with p53 mutations

circPCMTD1 is a novel target in p53 mutated leukemias.

The Need

Despite recent progress in understanding acute myeloid leukemia (AML) biology and the use of intensive treatments, the long-term overall survival of non-pediatric AML patients is only 30-40% in young patients (<60 years) and less than 10% in elderly AML patients (>60 years). This highlights the urgent need for novel therapeutic approaches for adult AML patients.


Circular RNA (circRNA) is characterized by perturbed arrangement of exons that lack a poly-A tail and are generally believed to lack protein coding potential. circRNAs can sequester microRNAs (miRs) and function as miR sponges, consequently acting as global regulators of cellular processes in cancer cells.

The Technology

Researchers at The Ohio State University, led by Dr. Ramiro Garzon, have discovered a prognostic and biological function of circular PCMTD1 (circPCMTD1) in leukemia. The inventors demonstrated that high expression of circPCMTD1 in AML patients significantly correlates with poorer clinical outcomes, whereas expression of linear PCMTD1 (linPCMTD1) is not a prognostic indicator. Despite traditional dogma that circRNAs lack protein coding potential, the inventors surprisingly discovered a novel 35kD protein translated from circPCMTD1. Using an anti-circPCMTD1gapmer to target circular, but not linPCMTD1, the inventors showed that knockdown of circPCMTD1 eliminates expression of the 35kD protein and impairs DNA replication by preventing the formation of the BTR complex, which plays a critical role in DNA replication and repair. AML cells experienced a significant increase in G2/M cell cycle arrest following circPCMTD1 knockdown, an effect that was rescued using a peptide sequence identified in the circPCMTD1 open reading frame. Together, these studies suggest circPCMTD1 is indispensable for the proliferation of leukemic myeloblasts and targeting the circPCMTD1 RNA or circPCMTD1-derived protein may be an effective therapeutic approach for AML patients.


  • Personalized medicine
  • Companion diagnostic compatible technology
  • Novel target
  • Cancer-specific target
  • Therapeutic antibody development opportunity
  • Therapeutic gapmer or anti-sense oligonucleotide development opportunity

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