Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia Journal Article


Authors: Xiao, W.; Chan, A.; Waarts, M. R.; Mishra, T.; Liu, Y.; Cai, S. F.; Yao, J.; Gao, Q.; Bowman, R. L.; Koche, R. P.; Csete, I. S.; DelGaudio, N. L.; Derkach, A.; Baik, J.; Yanis, S.; Famulare, C. A.; Patel, M.; Arcila, M. E.; Stahl, M.; Rampal, R. K.; Tallman, M. S.; Zhang, Y.; Dogan, A.; Goldberg, A. D.; Roshal, M.; Levine, R. L.
Article Title: Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia
Abstract: Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon-producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia. The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here, we characterize patients with AML with pDC expansion (pDC-AML), which we observe in similar to 5% of AML cases. pDC-AMLs often possess cross-lineage antigen expression and have adverse risk stratification with poor outcome. RUNX1 mutations are the most common somatic alterations in pDC-AML (>70%) and are much more common than in AML without pDC expansion and BPDCN. We demonstrate that pDCs are clonally related to, as well as originate from, leukemic blasts in pDC-AML. We further demonstrate that leukemic blasts from RUNX1-mutated AML upregulate a pDC transcriptional program, poising the cells toward pDC differentiation and expansion. Finally, tagraxofusp, a targeted therapy directed to CD123, reduces leukemic burden and eliminates pDCs in a patient-derived xenograft model. In conclusion, pDC-AML is characterized by a high frequency of RUNX1 mutations and increased expression of a pDC transcriptional program. CD123 targeting represents a potential treatment approach for pDC-AML.
Journal Title: Blood
Volume: 137
Issue: 10
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2021-03-11
Start Page: 1377
End Page: 1391
Language: English
ACCESSION: WOS:000646099500017
DOI: 10.1182/blood.2020007897
PROVIDER: wos
PMCID: PMC7955409
PUBMED: 32871587
Notes: Article -- Source: Wos
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MSK Authors
  1. Martin Stuart Tallman
    649 Tallman
  2. Jinjuan Yao
    59 Yao
  3. Raajit Kumar Rampal
    338 Rampal
  4. Ross Levine
    776 Levine
  5. Maria Eugenia Arcila
    660 Arcila
  6. Sheng Feng Cai
    45 Cai
  7. Minal A Patel
    70 Patel
  8. Robert L Bowman
    52 Bowman
  9. Ahmet Dogan
    455 Dogan
  10. Richard Patrick Koche
    174 Koche
  11. Mikhail Roshal
    230 Roshal
  12. Qi   Gao
    66 Gao
  13. Aaron David Goldberg
    106 Goldberg
  14. Alexander Yoshifumi Chan
    42 Chan
  15. Yanming Zhang
    199 Zhang
  16. Wenbin Xiao
    108 Xiao
  17. Jee Yeon Baik
    44 Baik
  18. Maximilian Stahl
    42 Stahl
  19. Ying Liu
    33 Liu
  20. Isabelle Sara Csete
    9 Csete
  21. Andriy Derkach
    148 Derkach
  22. Tanmay Mishra
    10 Mishra
  23. Michael R Waarts
    8 Waarts
  24. Sophia N. Yanis
    1 Yanis