Ethical issues on the "synthetic" phosphoethanolamine clinical trial.
- Francisco José Roma Paumgartten
- Revista da Associacao Medica Brasileira
Background:We recently showed that synthetic phosphoethanolamine reduces tumour growth and inhibits lung metastasis in vivo. Here, we investigated its anti-leukaemia effects using acute promyelocytic leukaemia (APL) as a model.Methods:Cytotoxic effects of Pho-s on leukaemia cells were evaluated by MTT assay. Leukaemic cells obtained from hCG-PML-RARa transgenic mice were transplanted to NOD/SCID mice. After the animals were diagnosed as leukaemic, treatment started with Pho-s using all-trans retinoid acid or daunorubicin as positive control or and saline control. Cell morphology and immunophenotyping were used to detect the undifferentiated blast cells in the spleen, liver and bone marrow. The induction of apoptosis in vitro and in malignant leukaemic clones was evaluated.Results:Synthetic phosphoethanolamine is cytotoxic and induces apoptosis through the mitochondrial pathway in vitro to leukaemia cell lines. In vivo Pho-s exhibits anti-proliferative effects in APL model reducing the number of CD117+ and Gr-1+ immature myeloid cells in the BM, spleen and liver. Synthetic phosphoethanolamine impairs the expansion of malignant clones CD34+/CD117+, CD34+ and Gr-1+ in the BM. In addition, Pho-s induces apoptosis of immature cells in the spleen and liver, a notable effect.Conclusion:Synthetic phosphoethanolamine has anti-leukaemic effects in an APL model by inhibiting malignant clone expansion, suggesting that it is an interesting compound for leukaemia treatment.