Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response

Kana Sakamoto, Ryohei Katayama, Reimi Asaka, Seiji Sakata, Satoko Baba, Hideki Nakasone, Sumie Koike, Naoko Tsuyama, Akito Dobashi, Makoto Sasaki, Ryo Ichinohasama, Emi Takakuwa, Rie Yamazaki, Jun Takizawa, Takahiro Maeda, Miwako Narita, Koji Izutsu, Yoshinobu Kanda, Koichi Ohshima, Kengo Takeuchi

Research output: Contribution to journalArticle

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Abstract

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%) MYCBPDCN (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 MYCBPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYCBPDCN) 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 MYCBPDCN, 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.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalLeukemia
DOIs
Publication statusAccepted/In press - 2018 May 23

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Dendritic Cells
Pharmaceutical Preparations
Neoplasms
Aurora Kinases
Precision Medicine
Skin
Hematologic Neoplasms
Protein Kinases
Small Interfering RNA
Cell Line
Growth

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm : association with immunoblastoid cytomorphology, MYC expression, and drug response. / Sakamoto, Kana; Katayama, Ryohei; Asaka, Reimi; Sakata, Seiji; Baba, Satoko; Nakasone, Hideki; Koike, Sumie; Tsuyama, Naoko; Dobashi, Akito; Sasaki, Makoto; Ichinohasama, Ryo; Takakuwa, Emi; Yamazaki, Rie; Takizawa, Jun; Maeda, Takahiro; Narita, Miwako; Izutsu, Koji; Kanda, Yoshinobu; Ohshima, Koichi; Takeuchi, Kengo.

In: Leukemia, 23.05.2018, p. 1-14.

Research output: Contribution to journalArticle

Sakamoto, K, Katayama, R, Asaka, R, Sakata, S, Baba, S, Nakasone, H, Koike, S, Tsuyama, N, Dobashi, A, Sasaki, M, Ichinohasama, R, Takakuwa, E, Yamazaki, R, Takizawa, J, Maeda, T, Narita, M, Izutsu, K, Kanda, Y, Ohshima, K & Takeuchi, K 2018, 'Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response', Leukemia, pp. 1-14. https://doi.org/10.1038/s41375-018-0154-5
Sakamoto, Kana ; Katayama, Ryohei ; Asaka, Reimi ; Sakata, Seiji ; Baba, Satoko ; Nakasone, Hideki ; Koike, Sumie ; Tsuyama, Naoko ; Dobashi, Akito ; Sasaki, Makoto ; Ichinohasama, Ryo ; Takakuwa, Emi ; Yamazaki, Rie ; Takizawa, Jun ; Maeda, Takahiro ; Narita, Miwako ; Izutsu, Koji ; Kanda, Yoshinobu ; Ohshima, Koichi ; Takeuchi, Kengo. / Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm : association with immunoblastoid cytomorphology, MYC expression, and drug response. In: Leukemia. 2018 ; pp. 1-14.
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abstract = "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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AU - Sakamoto, Kana

AU - Katayama, Ryohei

AU - Asaka, Reimi

AU - Sakata, Seiji

AU - Baba, Satoko

AU - Nakasone, Hideki

AU - Koike, Sumie

AU - Tsuyama, Naoko

AU - Dobashi, Akito

AU - Sasaki, Makoto

AU - Ichinohasama, Ryo

AU - Takakuwa, Emi

AU - Yamazaki, Rie

AU - Takizawa, Jun

AU - Maeda, Takahiro

AU - Narita, Miwako

AU - Izutsu, Koji

AU - Kanda, Yoshinobu

AU - Ohshima, Koichi

AU - Takeuchi, Kengo

PY - 2018/5/23

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N2 - 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.

AB - 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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