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CYTOGENETICS AND MOLECULAR GENETICS

Bone marrow clonal hematopoiesis is highly prevalent in blastic plasmacytoid dendritic cell neoplasm and frequently sharing a clonal origin in elderly patients

Leukemia volume 36, pages 1343–1350 (2022)Cite this article

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Abstract

Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are reported in up to 20% patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), where a shared clonal origin is shown in individual case studies. In this study, we performed targeted next generating sequencing on multiple bone marrow (BM), skin or sorted cells from 51 BPDCN patients (68.7 years,14.4–84.7), and detected mutations in BM hematopoietic cells in 65% (30/46) and BPDCN in 100% (27/27), both components showing similar high frequencies of TET2 (60% versus 58%) and ASXL1 (33% versus 40%). Of 24 patients with paired mutation data, 13(54%) had shared mutations, with TET2(77%), ASXL1(37%) and ZRSR2(22%) the most commonly shared, and NRAS the most gained mutation in BPDCN(9/24, 38%). Karyotypic abnormalities were detected in 19/29(66%) BPDCN but only in 1/49 BM hematopoietic cells, providing additional evidence of clonal evolution. BM clonal hematopoiesis (CH) was associated with an older age (p < 0.001), being confounding factors in multivariate analysis; whereas <10% BM BPDCN infiltrate and stem cell transplant were associated with favorable outcomes. This study is the first to report a high prevalence of BM CH in BPDCN patients beyond an associated diagnosis of MDS/CMML, and demonstrates a frequent clonal relationship in elderly, findings contributing to the understanding of BPDCN clonal origin.

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Fig. 1: Column chart depicting the relative frequency of mutations.
Fig. 2: Clonal relations between bone marrow hematopoietic cells and blastic plasmacytoid dendritic neoplasm (BPDCN).
Fig. 3: Overall survival (OS) comparison by Kaplan–Meier log-rank test.

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Author notes

  1. Mahsa Khanlari

    Present address: Department of Pathology and the Hematological Malignancies Program, St. Jude Children’s Research Hospital, Memphis, TN, USA

Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Mahsa Khanlari, C. Cameron Yin, Guilin Tang, Sanam Loghavi, Ismael Bah, Wei Wang, Sergej Konoplev, L. Jeffrey Medeiros, Joseph D. Khoury & Sa A. Wang

  2. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Koichi Takahashi & Naveen Pemmaraju

  3. Department of Pathology and the Hematological Malignancies Program, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Curtis Lachowiez

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Contributions

MK, SAW, CCY, GT, IB, WW, SK, and CL: data collection and analysis, figures and tables. MK, KT, JDK, SL, CCY, WW, and SAW: NGS testing, interpretation and flow cytometry analysis. NP and KT: clinical data, treatment and clinical outcome analysis. SAW, MK, and LJM: manuscript writing. SAW, JDK, NP, and LJM: experiment design. All authors have read and approved the manuscript.

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Correspondence to Sa A. Wang.

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Khanlari, M., Yin, C.C., Takahashi, K. et al. Bone marrow clonal hematopoiesis is highly prevalent in blastic plasmacytoid dendritic cell neoplasm and frequently sharing a clonal origin in elderly patients. Leukemia 36, 1343–1350 (2022). https://doi.org/10.1038/s41375-022-01538-9

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