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Response to letter from Dr Domenico Ribatti

Leukemia volume 16, page 1891 (2002)Cite this article

As Dr Ribatti indicates, our recent brief report in Blood1 described a patient with a myelodysplastic syndrome (MDS) who developed acute monoblastic leukemia (acute myeloid leukemia (AML), French–American–British type M5a) shortly after initiating erythropoietin (EPO) therapy, and in whom AML regressed rapidly following discontinuation of EPO. The patient's AML cells expressed the EPO receptor and proliferated in vitro in response to EPO. We concluded that leukemic transformation was EPO-dependent in this patient, and that the mechanism of transformation was proliferation of myeloid blasts in response to EPO.

Dr Ribatti proposes a second mechanism by which EPO therapy in MDS may promote progression to AML. He has previously reported that EPO promotes angiogenesis in vitro and in vivo by binding to EPO receptors present on vascular endothelial cells and stimulating their proliferation.2 There is ample evidence that angiogenesis is important in MDS and AML. Bone marrow microvessel density is increased in MDS and AML and correlates with the percentage of myeloblasts, suggesting a correlation between angiogenesis and progression to leukemia.3 Additional evidence for the importance of angiogenesis in MDS is the documentation of therapeutic responses to the anti-angiogenic agent thalidomide.4 Thus, EPO therapy in MDS has the potential to promote angiogenesis in the bone marrow, which could in turn stimulate blast proliferation and evolution to acute leukemia.

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References

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  1. Roswell Park Cancer Institute, Buffalo, NY, USA

    U Bunworasate, H Arnouk, H Minderman, KL O'Loughlin, SNJ Sait, M Barcos, CC Stewart & MR Baer

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  1. U Bunworasate
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  2. H Arnouk
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Bunworasate, U., Arnouk, H., Minderman, H. et al. Response to letter from Dr Domenico Ribatti. Leukemia 16, 1891 (2002). https://doi.org/10.1038/sj.leu.2402624

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