Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Chronic myeloproliferative neoplasms

Azacitidine is effective for targeting leukemia-initiating cells in juvenile myelomonocytic leukemia

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2


  1. 1.

    Niemeyer CM, Locatelli F. Chronic myeloproliferative disorders. In: Pui CH, editor. Childhood leukemias. 3rd ed. New York: Cambridge University Press; 2012. p. 444–502.

    Google Scholar 

  2. 2.

    Flotho C, Valcamonica S, Mach-Pascual S, Schmahl G, Corral L, Ritterbach J, et al. RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia. 1999;13:32–37.

    CAS  Article  Google Scholar 

  3. 3.

    Locatelli F, Niemeyer CM. How I treat juvenile myelomonocytic leukemia. Blood. 2015;125:1083–90.

    CAS  Article  Google Scholar 

  4. 4.

    Olk-Batz C, Poetsch AR, Nöllke P, Claus R, Zucknick M, Sandrock I, et al. Aberrant DNA methylation characterizes juvenile myelomonocytic leukemia (JMML) with poor outcome. Blood. 2011;117:4871–80.

    CAS  Article  Google Scholar 

  5. 5.

    Lipka DB, Witte T, Toth R, Yang J, Wiesenfarth M, Nöllke P, et al. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nat Commun. 2017;8:2126.

    Article  Google Scholar 

  6. 6.

    Stieglitz E, Mazor T, Olshen AB, Geng H, Gelston LC, Akutagawa J, et al. Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia. Nat Commun. 2017;8:2127.

    Article  Google Scholar 

  7. 7.

    Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, et al. Integrated molecular profiling of juvenile myelomonocytic leukemia. Blood. 2018;131:1576–86.

    CAS  Article  Google Scholar 

  8. 8.

    Cseh A, Niemeyer CM, Yoshimi A, Dworzak M, Hasle H, van den Heuvel-Eibrink MM, et al. Bridging to transplant with azacitidine in juvenile myelomonocytic leukemia: a retrospective analysis of the EWOG-MDS study group. Blood. 2015;125:2311–3.

    Article  Google Scholar 

  9. 9.

    Krombholz CF, Aumann K, Kollek M, Bertele D, Fluhr S, Kunze M, et al. Long-term serial xenotransplantation of juvenile myelomonocytic leukemia recapitulates human disease in Rag2-/-gammac-/- mice. Haematologica. 2016;101:597–606.

    Article  Google Scholar 

  10. 10.

    Flotho C, Sommer S, Lübbert M. DNA-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia. Semin Cancer Biol. 2018;51:68–79.

    CAS  Article  Google Scholar 

  11. 11.

    Roulois D, Loo YH, Singhania R, Wang Y, Danesh A, Shen SY, et al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell. 2015;162:961–73.

    CAS  Article  Google Scholar 

  12. 12.

    Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell. 2015;162:974–86.

    CAS  Article  Google Scholar 

  13. 13.

    Brocks D, Schmidt CR, Daskalakis M, Jang HS, Shah NM, Li D, et al. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat Genet. 2017;49:1052–60.

    CAS  Article  Google Scholar 

  14. 14.

    Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, Ryan G, et al. Induction of a CD8+T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 2010;116:1908–18.

    CAS  Article  Google Scholar 

  15. 15.

    Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget. 2014;5:587–98.

    PubMed  PubMed Central  Google Scholar 

Download references


This work was supported by the German Research Foundation (FOR2036 ER599/3-2 to M.E., CRC992-C05 and SPP1463 FL345/4-2 to C.F.).

Author information



Corresponding author

Correspondence to Christian Flotho.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

These authors contributed equally: Miriam Erlacher, Christian Flotho

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Krombholz, C.F., Gallego-Villar, L., Sahoo, S.S. et al. Azacitidine is effective for targeting leukemia-initiating cells in juvenile myelomonocytic leukemia. Leukemia 33, 1805–1810 (2019).

Download citation

Further reading


Quick links