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Expression of retinoic acid receptor–target genes during retinoic acid therapy for acute promyelocytic leukemia

Leukemia volume 17, pages 646–648 (2003)Cite this article

TO THE EDITOR

All-trans retinoic acid (ATRA) is a metabolite of vitamin A and plays an important role in cell differentiation, proliferation, reproduction, and development. Recently, ATRA has been used in differentiation therapy for acute promyelocytic leukemia (APL). APL is a subtype of myeloid leukemia with a translocation between chromosomes 15 and 17, resulting in a fusion protein between PML and retinoic acid receptor (RAR)α.1 ATRA therapy induces a high rate of complete remission without severe side effects. However, most patients who relapse after ATRA therapy have acquired ATRA resistance. This resistance seems to result from an insufficiently high plasma ATRA concentration during therapy. This phenomenon may be caused by the increased oxidative catabolism of ATRA by cytochrome P-450, increases in levels of cellular retinoic acid binding protein (CRABP), or multidrug-resistance (MDR) gene product. It may also be the result of some other cellular mechanism, as mutations in the RARα region of the PML/RARα fusion gene have been found in APL patients who relapse.

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Acknowledgements

We thank Mr Suzuki for performing statistical analyses. We also are grateful to Mr Ueno and Ms Kobayashi for their technical assistance.

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Authors and Affiliations

  1. Department of Pediatrics, Osaka, Japan

    K Takitani, M Koh, C L Zhu, A Inoue, T Kuno, H Tanoue, M Miyake & H Tamai

  2. Department of Clinical Pathology, Osaka Medical College, Osaka, Japan

    T Nakagawa

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  1. K Takitani
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  2. M Koh
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Takitani, K., Koh, M., Zhu, C. et al. Expression of retinoic acid receptor–target genes during retinoic acid therapy for acute promyelocytic leukemia. Leukemia 17, 646–648 (2003). https://doi.org/10.1038/sj.leu.2402818

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