Divergent clonal evolution of blastic plasmacytoid dendritic cell neoplasm and chronic myelomonocytic leukemia from a shared TET2-mutated origin.
Divergent clonal evolution of blastic plasmacytoid dendritic cell neoplasm and chronic myelomonocytic leukemia from a shared TET2-mutated origin.
复制标题
DOI：
10.1038/s41375-021-01228-y
复制
发表时间：
2021-11
期刊：
影响因子：
11.4
通讯作者：
Wiseman DH
中科院分区：
文献类型：
--
作者：
Batta K;Bossenbroek HM;Pemmaraju N;Wilks DP;Chasty R;Dennis M;Milne P;Collin M;Beird HC;Taylor J;Patnaik MM;Cargo CA;Somervaille TCP;Wiseman DH
母细胞性浆细胞样树突状细胞肿瘤（BPDCN）是一种罕见的皮肤病性血液恶性肿瘤，源自浆细胞样树突状细胞（pDC）前体。在 > 20% 的病例中，它与其他骨髓恶性肿瘤共存，尤其经常与慢性粒单核细胞白血病 (CMML) 共存[1]。鉴于共享克隆起源的新数据 [2, 3] 和表征 CMML 微环境的支持性克隆 pDC [4]，这些疾病可能具有共同的生物学和治疗弱点。然而，它们详细的基因组图谱、克隆关系和独特的发病机制仍不清楚。一名 73 岁男性出现躯干和四肢广泛的紫癜病变（补充图 1）。十年前，他被诊断出患有低风险 CMML-0，并通过主动监测进行全程管理。皮肤活检证实 BPDCN，中度增殖 (Ki67 50%) 母细胞浸润，表达经典诊断三联体 CD4、CD56 和 CD123 [1]，以及 BCL2、CD10、CD33、TdT 和 CD99。血细胞计数显示稳定的单核细胞增多（1.4×109/L）和中性粒细胞减少（1.4×109/L），但血小板计数正常。骨髓 (BM) 被 CMML 严重浸润，具有细胞过多、发育不良的骨髓单核细胞前体，但没有原始细胞/幼单核细胞过多。 BM 流式细胞术显示 26% CD64+ CD14+ 单核细胞、1% CD34+ 成髓细胞和 1% 肿瘤性 pDC（CD4+ CD56+ CD123+ HLA-DR+ NG2+），表明 BPDCN 参与程度较低。核型正常。开始使用阿扎胞苷进行非强化治疗。三个周期后皮损保持不变。 BM 显示 CMML 消退，但现在 BPDCN 广泛参与（> 70%）。阿扎胞苷已停用，并接受支持性护理。不久后，他出现中枢视力丧失并伴有脉络膜浸润，表明中枢神经系统受损
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare dermatopathic hematological malignancy derived from plasmacytoid dendritic cell (pDC) precursors. It co-exists with other myeloid malignancies in> 20% of cases, and especially frequently with chronic myelomonocytic leukemia (CMML)[1]. Given emerging data for shared clonal origin [2, 3] and supportive clonal pDCs characterizing the CMML microenvironment [4], these diseases might share common biology and therapeutic vulnerabilities. However, their detailed genomic landscape, clonal relationship, and distinctive pathogenesis remain unclear. A 73-year-old male presented with widespread purpuric lesions over trunk and limbs (Supplementary Fig. 1). Ten years earlier he was diagnosed with low-risk CMML-0, managed throughout by active surveillance. Skin biopsy confirmed BPDCN, with infiltration by moderately proliferative (Ki67 50%) blasts expressing the classic diagnostic triad of CD4, CD56, and CD123 [1], alongside BCL2, CD10, CD33, TdT, and CD99. Blood count revealed a stable monocytosis (1.4× 109/L) and neutropenia (1.4× 109/L), but a normal platelet count. Bone marrow (BM) was heavily infiltrated by CMML, with hypercellular, dysplastic myelomonocytic precursors but no blast/promonocyte excess. Flow cytometry of BM revealed 26% CD64+ CD14+ monocytes, 1% CD34+ myeloblasts, and 1% neoplastic pDCs (CD4+ CD56+ CD123+ HLA-DR+ NG2+), indicating low-level BPDCN involvement. Karyotype was normal. Non-intensive treatment with azacitidine was commenced. After three cycles skin lesions remained unchanged. BM showed regression of CMML but now extensive (> 70%) involvement by BPDCN. Azacitidine was discontinued and he was managed with supportive care. Shortly after he developed central visual loss with choroidal infiltrates, indicating central nervous system
登录
查看更多内容
影响因子：
5.6
作者：
Costa V;Righelli D;Russo F;De Berardinis P;Angelini C;D'Apice L
通讯作者：
D'Apice L
影响因子：
5.9
作者：
Ostrander, Elizabeth L.;Kramer, Ashley C.;Challen, Grant A.
通讯作者：
Challen, Grant A.
影响因子：
6.5
作者：
Berggren, Daniel Moreno;Folkvaljon, Yasin;Ejerblad, Elisabeth
通讯作者：
Ejerblad, Elisabeth
影响因子：
12.8
作者：
Beird, Hannah C.;Khan, Maliha;Pemmaraju, Naveen
通讯作者：
Pemmaraju, Naveen
影响因子：
2.7
作者：
Gao, Na;Wang, Xue-Xia;Guo, Nong-Jian
通讯作者：
Guo, Nong-Jian