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
PMCID: PMC7955409
PUBMED: 32871587
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. Martin Stuart Tallman
    562 Tallman
  2. Jinjuan Yao
    41 Yao
  3. Raajit Kumar Rampal
    197 Rampal
  4. Ross Levine
    611 Levine
  5. Maria Eugenia Arcila
    523 Arcila
  6. Sheng Feng Cai
    21 Cai
  7. Minal A Patel
    62 Patel
  8. Robert L Bowman
    34 Bowman
  9. Ahmet Dogan
    286 Dogan
  10. Richard Patrick Koche
    89 Koche
  11. Mikhail Roshal
    145 Roshal
  12. Qi   Gao
    31 Gao
  13. Alexander Yoshifumi Chan
    17 Chan
  14. Yanming Zhang
    98 Zhang
  15. Wenbin Xiao
    51 Xiao
  16. Jee Yeon Baik
    24 Baik
  17. Maximilian Stahl
    21 Stahl
  18. Ying Liu
    12 Liu
  19. Isabelle Sara Csete
    5 Csete
  20. Andriy Derkach
    13 Derkach
  21. Tanmay Mishra
    2 Mishra
  22. Michael R Waarts
    1 Waarts
  23. Sophia N. Yanis
    1 Yanis