Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) cases showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYC−BPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYC−BPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYC−BPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extra-terminal protein (BETis), and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYC−BPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN, in accordance with precision medicine.
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This work was supported in part by grants from AMED (16cm0106203h0001 to RK and 17cm0106501h0002 to KT) and MEXT/JSPS KAKENHI (17K18338 to KS and 16H04715 to RK). The authors thank the many physicians of the cooperating institutions (listed in the online material) for providing the specimens and clinical data. The authors also thank Ms. Saki Yoshino, Ms. Sayuri Amino, Dr. Seiichi Mori, Ms. Keiko Shiozawa, Mr. Motoyoshi Iwakoshi, Ms. Tomoyo Kakita, and Ms. Yuki Togashi of the Japanese Foundation for Cancer Research for their technical support, and Ms. Sayuri Sengoku and Ms. Hiroko Nozaki for administrative assistance.
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The authors declare that they have no conflict of interest.
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Sakamoto, K., Katayama, R., Asaka, R. et al. Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response. Leukemia 32, 2590–2603 (2018). https://doi.org/10.1038/s41375-018-0154-5
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