Casiopeina III-Ea, a copper-containing small molecule, inhibits the in vitro growth of primitive hematopoietic cells from chronic myeloid leukemia

- Chronic Myeloid Leukemia is initiated and sustained by BCR-ABL+ leukemia stem cells.
- Quiescent Leukemic Stem Cells are insensitive to BCR-ABL Tyrosine Kinase Inhibitors.
- Casiopeinas are novel small molecules with anticancer activity.
- Casiopeina III-Ea possesses antileukemic activity in vitro with minimal effects on normal cells.

Several novel compounds have been developed for the treatment of different types of leukemia. In the present study, we have assessed the in vitro effects of Casiopeina III-Ea, a copper-containing small molecule, on cells from patients with Chronic Myeloid Leukemia (CML). We included primary CD34+ Lineage-negative (Lin−) cells selected from CML bone marrow, as well as the K562 and MEG01 cell lines. Bone marrow cells obtained from normal individuals - both total mononuclear cells as well as CD34+ Lin− cells- were used as controls. IC50 corresponded to 0.5 μM for K562 cells, 0.63 μM for MEG01 cells, 0.38 μM for CML CD34+ lin− cells, and 1.0 μM for normal CD34+ lin− cells. Proliferation and expansion were also inhibited to significantly higher extents in cultures of CML cells as compared to their normal counterparts. All these effects seemed to occur via a bcr-abl transcription-independent mechanism that involved a delay in cell division, an increase in cell death, generation of Reactive Oxygen Species and changes in cell cycle. Our results demonstrate that Casiopeina III-Ea possesses strong antileukemic activity in vitro, and warrant further preclinical (animal) studies to assess such effects in vivo.