Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan;70(1):83-97.
doi: 10.1369/00221554211062499.

IDH1/2 Mutations in Cancer Stem Cells and Their Implications for Differentiation Therapy

Remco J Molenaar  1   2 , Johanna W Wilmink  2
Affiliations
Review

IDH1/2 Mutations in Cancer Stem Cells and Their Implications for Differentiation Therapy

Remco J Molenaar et al. J Histochem Cytochem. 2022 Jan.

Abstract

Isocitrate dehydrogenase 1 and 2 (IDH1/2) are enzymes recurrently mutated in various types of cancer, including glioma, cholangiocarcinoma, chondrosarcoma, and acute myeloid leukemia. Mutant IDH1/2 induce a block in differentiation and thereby contribute to the stemness and oncogenesis of their cells of origin. Recently, small-molecule inhibitors of mutant IDH1/2 have been Food and Drug Administration-approved for the treatment of IDH1/2-mutated acute myeloid leukemia. These inhibitors decrease the stemness of the targeted IDH1/2-mutated cancer cells and induce their differentiation to more mature cells. In this review, we elucidate the mechanisms by which mutant IDH1/2 induce a block in differentiation and the biological and clinical effects of the release into differentiation by mutant-IDH1/2 inhibitors. (J Histochem Cytochem 70:83-97, 2022).

Keywords: 2-hydroxyglutarate; cancer stem cells; chemotherapy; differentiation; enasidenib; isocitrate dehydrogenase; ivosidenib; targeted therapy; therapy responses.

PubMed Disclaimer

Conflict of interest statement

Competing interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rosen JM, Jordan CT. The increasing complexity of the cancer stem cell paradigm. Science. 2009;324(5935):1670–3. doi:10.1126/science.1171837. - DOI - PMC - PubMed
    1. Molenaar RJ, Radivoyevitch T, Maciejewski JP, van Noorden CJ, Bleeker FE. The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation. Biochim Biophys Acta. 2014. Dec;1846(2):326–41. doi:10.1016/j.bbcan.2014.05.004. - DOI - PubMed
    1. Atai NA, Renkema-Mills NA, Bosman J, Schmidt N, Rijkeboer D, Tigchelaar W, Bosch KS, Troost D, Jonker A, Bleeker FE, Miletic H, Bjerkvig R, De Witt Hamer PC, Van Noorden CJ. Differential activity of NADPH-producing dehydrogenases renders rodents unsuitable models to study IDH1R132 mutation effects in human glioblastoma. J Histochem Cytochem. 2011. May;59(5):489–503. doi:10.1369/0022155411400606. - DOI - PMC - PubMed
    1. Bleeker FE, Atai NA, Lamba S, Jonker A, Rijkeboer D, Bosch KS, Tigchelaar W, Troost D, Vandertop WP, Bardelli A, Van Noorden CJ. The prognostic IDH1(R132) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma. Acta Neuropathol. 2010. Apr;119(4):487–94. doi:10.1007/s00401-010-0645-6. - DOI - PMC - PubMed
    1. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009. Dec 10;462(7274):739–44. doi:10.1038/nature08617. - DOI - PMC - PubMed

Publication types

MeSH terms