Blastic Plasmacytoid Dendritic Cell Neoplasm: Progress in Cell Origin, Molecular Biology, Diagnostic Criteria and Therapeutic Approaches

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with poor overall survival. BPDCN is derived from plasmacytoid dendritic cells (pDCs) and its pathogenesis is unclear. The tumor cells show aberrant expression of CD4, CD56, interleukin-3 receptor alpha chain (CD123), blood dendritic cell antigen 2 (BDCA 2/CD303), blood dendritic cell antigen 4 (BDCA4) and transcription factor (E protein) E2-2 (TCF4). The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma. Relapse with drug resistance generally occurs quickly. Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy. In this review, we summarize the differentiation of BPDCN from its cell origin, its connection with normal pDCs, clinical characteristics, genetic mutations and advances in treatment of BPDCN. This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.

Keywords

blastic plasmacytoid dendritic cell neoplasm / plasmacytoid dendritic cell / genetic mutations / immunophenotype / therapeutics

References

[1] AdachiM, MaedaK, TakekawaM, et al.. High expression of CD56 (N-CAM) in a patient with cutaneous CD4-positive lymphoma. Am J Hematol, 1994, 47(4): 278-282

[2] BrodyJP, AllenS, SchulmanP, et al.. Acute agranular CD4-positive natural killer cell leukemia. Comprehensive clinicopathologic studies including virologic and in vitro culture with inducing agents. Cancer, 1995, 75(10): 2474-2483

[3] PetrellaT, DalacS, MaynadiéM, et al.. CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Français d’Etude des Lymphomes Cutanés (GFELC). Am J Surg Pathol, 1999, 23(2): 137-146

[4] AoyamaY, YamaneT, HinoM, et al.. Blastic NK-cell lymphoma/leukemia with T-cell receptor gamma rearrangement. Ann Hematol, 2001, 80(12): 752-754

[5] VardimanJW, ThieleJ, ArberDA, et al.. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 2009, 114(5): 937-951

[6] ArberDA, OraziA, HasserjianR, et al.. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016, 127(20): 2391-2405

[7] ChaperotL, BendrissN, ManchesO, et al.. Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood, 2001, 97(10): 3210-3217

[8] FeuillardJ, JacobMC, ValensiF, et al.. Clinical and biologic features of CD4(+)CD56(+) malignancies. Blood, 2002, 99(5): 1556-1563

[9] PetrellaT, ComeauMR, MaynadiéM, et al.. ‘Agranular CD4+ CD56+ hematodermic neoplasm’ (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol, 2002, 26(7): 852-862

[10] JacobMC, ChaperotL, MossuzP, et al.. CD4+ CD56+ lineage negative malignancies: a new entity developed from malignant early plasmacytoid dendritic cells. Haematologica, 2003, 88(8): 941-955

[11] DzionekA, SohmaY, NagafuneJ, et al.. BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction. J Exp Med, 2001, 194(12): 1823-1834

[12] HerlingM, TeitellMA, ShenRR, et al.. TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin. Blood, 2003, 101(12): 5007-5009

[13] JayeDL, GeigermanCM, HerlingM, et al.. Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms. Mod Pathol, 2006, 19(12): 1555-1562

[14] MarafiotiT, PatersonJC, BallabioE, et al.. Novel markers of normal and neoplastic human plasmacytoid dendritic cells. Blood, 2008, 111(7): 3778-3792

[15] SasakiI, HoshinoK, SugiyamaT, et al.. Spi-B is critical for plasmacytoid dendritic cell function and development. Blood, 2012, 120(24): 4733-4743

[16] BoiocchiL, LonardiS, VermiW, et al.. BDCA-2 (CD303): a highly specific marker for normal and neoplastic plasmacytoid dendritic cells. Blood, 2013, 122(2): 296-297

[17] Montes-MorenoS, Ramos-MedinaR, Martínez-LópezA, et al.. SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: characterization of its expression in major hematolymphoid neoplasms. Blood, 2013, 121(4): 643-647

[18] FacchettiF, CigognettiM, FisogniS, et al.. Neoplasms derived from plasmacytoid dendritic cells. Mod Pathol, 2016, 29(2): 98-111

[19] SapienzaMR, FuligniF, AgostinelliC, et al.. Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition. Leukemia, 2014, 28(8): 1606-1616

[20] LennertK, RemmeleW. Karyometric research on lymph node cells in man. I. Germinoblasts, lymphoblasts & lymphocytes. Acta Haematol, 1958, 19(2): 99-113

[21] FacchettiF, VermiW, MasonD, et al.. The plasmacytoid monocyte/interferon producing cells. Virchows Arch, 2003, 443(6): 703-717

[22] FacchettiF, de Wolf-PeetersC, MasonDY, et al.. Plasmacytoid T cells. Immunohistochemical evidence for their monocyte/macrophage origin. Am J Pathol, 1988, 133(1): 15-21

[23] CellaM, JarrossayD, FacchettiF, et al.. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med, 1999, 5(8): 919-923

[24] RissoanMC, SoumelisV, KadowakiN, et al.. Reciprocal control of T helper cell and dendritic cell differentiation. Science, 1999, 283(5405): 1183-1186

[25] SiegalFP, KadowakiN, ShodellM, et al.. The nature of the principal type 1 interferon-producing cells in human blood. Science, 1999, 284(5421): 1835-1837

[26] HaniffaM, CollinM, GinhouxF. Ontogeny and functional specialization of dendritic cells in human and mouse. Adv Immunol, 2013, 120: 1-49

[27] SoumelisV, LiuYJ. From plasmacytoid to dendritic cell: morphological and functional switches during plasmacytoid pre-dendritic cell differentiation. Eur J Immunol, 2006, 36(9): 2286-2292

[28] FacchettiF, De Wolf-PeetersC, van den OordJJ, et al.. Plasmacytoid T cells: a cell population normally present in the reactive lymph node. An immunohistochemical and electronmicroscopic study. Hum Pathol, 1988, 19(9): 1085-1092

[29] JingY, ShaheenE, DrakeRR, et al.. Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum Immunol, 2009, 70(10): 777-784

[30] JegalianAG, FacchettiF, JaffeES. Plasmacytoid dendritic cells: physiologic roles and pathologic states. Adv Anat Pathol, 2009, 16(6): 392-404

[31] VermiW, LonardiS, MorassiM, et al.. Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage. Immunobiology, 2009, 214(9–10): 877-886

[32] SozzaniS, VermiW, Del PreteA, et al.. Trafficking properties of plasmacytoid dendritic cells in health and disease. Trends Immunol, 2010, 31(7): 270-277

[33] VermiW, SonciniM, MelocchiL, et al.. Plasmacytoid dendritic cells and cancer. J Leukoc Biol, 2011, 90(4): 681-690

[34] FoggDK, SibonC, MiledC, et al.. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science, 2006, 311(5757): 83-87

[35] NaikSH, SatheP, ParkHY, et al.. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol, 2007, 8(11): 1217-1226

[36] OnaiN, Obata-OnaiA, SchmidMA, et al.. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol, 2007, 8(11): 1207-1216

[37] SatheP, MetcalfD, VremecD, et al.. Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor. Immunity, 2014, 41(1): 104-115

[38] LiuK, VictoraGD, SchwickertTA, et al.. In vivo analysis of dendritic cell development and homeostasis. Science, 2009, 324(5925): 392-397

[39] OnaiN, KurabayashiK, Hosoi-AmaikeM, et al.. A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential. Immunity, 2013, 38(5): 943-957

[40] MurphyTL, Grajales-ReyesGE, WuX, et al.. Transcriptional Control of Dendritic Cell Development. Annu Rev Immunol, 2016, 34: 93-119

[41] RodriguesPF, Alberti-ServeraL, EreminA, et al.. Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells. Nat Immunol, 2018, 19(7): 711-722

[42] ManzMG. Plasmacytoid dendritic cells: origin matters. Nat Immunol, 2018, 19(7): 652-654

[43] D’AmicoA, WuL. The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. J Exp Med, 2003, 198(2): 293-303

[44] KarsunkyH, MeradM, CozzioA, et al.. Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J Exp Med, 2003, 198(2): 305-313

[45] CisseB, CatonML, LehnerM, et al.. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell, 2008, 135(1): 37-48

[46] NagasawaM, SchmidlinH, HazekampMG, et al.. Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B. Eur J Immunol, 2008, 38(9): 2389-2400

[47] GhoshHS, CisseB, BuninA, et al.. Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity, 2010, 33(6): 905-916

[48] ReizisB. Regulation of plasmacytoid dendritic cell development. Curr Opin Immunol, 2010, 22(2): 206-211

[49] BelzGT, NuttSL. Transcriptional programming of the dendritic cell network. Nat Rev Immunol, 2012, 12(2): 101-113

[50] LiHS, YangCY, NallaparajuKC, et al.. The signal transducers STAT5 and STAT3 control expression of Id2 and E2-2 during dendritic cell development. Blood, 2012, 120(22): 4363-4673

[51] ColonnaM, TrinchieriG, LiuYJ. Plasmacytoid dendritic cells in immunity. Nat Immunol, 2004, 5(12): 1219-1226

[52] HondaK, YanaiH, NegishiH, et al.. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature, 2005, 434(7034): 772-777

[53] BlasiusAL, BeutlerB. Intracellular toll-like receptors. Immunity, 2010, 32(3): 305-315

[54] KawaiT, AkiraS. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol, 2010, 11(5): 373-384

[55] BeirdHC, KhanM, WangF, et al.. Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Blood Cancer J, 2019, 9(12): 99

[56] VillaniAC, SatijaR, ReynoldsG, et al.. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science, 2017, 356(6335): 1-31

[57] CeribelliM, HouZE, KellyPN, et al.. A Druggable TCF4- and BRD4-Dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm. Cancer Cell, 2016, 30(5): 764-778

[58] TangZ, TangG, WangSA, et al.. Simultaneous deletion of 3′ETV6 and 5′EWSR1 genes in blastic plasmacytoid dendritic cell neoplasm: case report and literature review. Mol Cytogenet, 2016, 9: 23

[59] LerouxD, MugneretF, CallananM, et al.. CD4(+), CD56(+) DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Français de Cytogénétique Hématologique. Blood, 2002, 99(11): 4154-4159

[60] DijkmanR, van DoornR, SzuhaiK, et al.. Geneexpression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities. Blood, 2007, 109(4): 1720-1727

[61] AlayedK, PatelKP, KonoplevS, et al.. TET2 mutations, myelodysplastic features, and a distinct immunoprofile characterize blastic plasmacytoid dendritic cell neoplasm in the bone marrow. Am J Hematol, 2013, 88(12): 1055-1061

[62] MenezesJ, AcquadroF, WisemanM, et al.. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia, 2014, 28(4): 823-829

[63] StenzingerA, EndrisV, PfarrN, et al.. Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm. Oncotarget, 2014, 5(15): 6404-6413

[64] SakamotoK, KatayamaR, AsakaR, et al.. Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response. Leukemia, 2018, 32(12): 2590-2603

[65] Sumarriva LezamaL, ChisholmKM, CarnealE, et al.. An analysis of blastic plasmacytoid dendritic cell neoplasm with translocations involving the MYC locus identifies t(6;8)(p21;q24) as a recurrent cytogenetic abnormality. Histopathology, 2018, 73(5): 767-776

[66] TangZ, LiY, WangW, et al.. Genomic aberrations involving 12p/ETV6 are highly prevalent in blastic plasmacytoid dendritic cell neoplasms and might represent early clonal events. Leuk Res, 2018, 73: 86-94

[67] ZhangX, SunJ, YangM, et al.. New perspectives in genetics and targeted therapy for blastic plasmacytoid dendritic cell neoplasm. Crit Rev Oncol Hematol, 2020, 149: 102928

[68] JardinF, CallananM, PentherD, et al.. Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease. Leukemia, 2009, 23(4): 698-707

[69] Abdel-WahabO, LevineRL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood, 2013, 121(18): 3563-3572

[70] LiM, ShahM, BinderM, et al.. Cutaneous blastic plasmacytoid dendritic cell neoplasm arising in the context of TET2 and ZRSR2 mutated clonal cytopenias of unknown significance, secondary to somatic copy number losses involving CDK2NA/2NB and MTAP. Am J Hematol, 2020, 95(2): E31-E34

[71] BuenoC, AlmeidaJ, LucioP, et al.. Incidence and characteristics of CD4(+)/HLA DRhi dendritic cell malignancies. Haematologica, 2004, 89(1): 58-69

[72] KhouryJD. Blastic Plasmacytoid Dendritic Cell Neoplasm. Curr Hematol Malig Rep, 2018, 13(6): 477-483

[73] Martín-MartínL, LópezA, VidrialesB, et al.. Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile. Oncotarget, 2015, 6(22): 19204-19216

[74] JuliaF, PetrellaT, Beylot-BarryM, et al.. Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients. Br J Dermatol, 2013, 169(3): 579-586

[75] PaganoL, ValentiniCG, PulsoniA, et al.. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study. Haematologica, 2013, 98(2): 239-246

[76] Martín-MartínL, AlmeidaJ, PomaresH, et al.. Blastic plasmacytoid dendritic cell neoplasm frequently shows occult central nervous system involvement at diagnosis and benefits from intrathecal therapy. Oncotarget, 2016, 7(9): 10174-10181

[77] FengZ, ZhouJ, BentleyG. Blastic plasmacytoid dendritic cell neoplasm: report of a case presenting with lung and central nervous system involvement and review of the literature. J La State Med Soc, 2014, 166(1): 2-9

[78] RauhMJ, RahmanF, GoodD, et al.. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation, lacking cutaneous involvement: Case series and literature review. Leuk Res, 2012, 36(1): 81-86

[79] WangH, CaoJ, HongX. Blastic plasmacytoid dendritic cell neoplasm without cutaneous lesion at presentation: case report and literature review. Acta Haematol, 2012, 127(2): 124-127

[80] KhouryJD, MedeirosLJ, ManningJT, et al.. CD56(+) TdT(+) blastic natural killer cell tumor of the skin: a primitive systemic malignancy related to myelomonocytic leukemia. Cancer, 2002, 94(9): 2401-2408

[81] CotaC, ValeE, VianaI, et al.. Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients. Am J Surg Pathol, 2010, 34(1): 75-87

[82] JuliaF, DalleS, DuruG, et al.. Blastic plasmacytoid dendritic cell neoplasms: clinico-immunohistochemical correlations in a series of 91 patients. Am J Surg Pathol, 2014, 38(5): 673-680

[83] PetrellaT, BagotM, WillemzeR, et al.. Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review. Am J Clin Pathol, 2005, 123(5): 662-675

[84] EmadaliA, HoghoughiN, DuleyS, et al.. Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms. Blood, 2016, 127(24): 3040-3053

[85] Garnache-OttouF, FeuillardJ, FerrandC, et al.. Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia. Br J Haematol, 2009, 145(5): 624-636

[86] DalleS, Beylot-BarryM, BagotM, et al.. Blastic plasmacytoid dendritic cell neoplasm: is transplantation the treatment of choice. Br J Dermatol, 2010, 162(1): 74-79

[87] Angelot-DelettreF, BiichleS, FerrandC, et al.. Intracytoplasmic detection of TCL1—but not ILT7-by flow cytometry is useful for blastic plasmacytoid dendritic cell leukemia diagnosis. Cytometry A, 2012, 81(8): 718-724

[88] SalvaKA, HaemelAK, PincusLB, et al.. Expression of CD31/PECAM-1 (platelet endothelial cell adhesion molecule 1) by blastic plasmacytoid dendritic cell neoplasms. JAMA Dermatol, 2014, 150(1): 73-76

[89] WangW, KhouryJD, MirandaRN, et al.. Immunophenotypic characterization of reactive and neoplastic plasmacytoid dendritic cells permits establishment of a 10-color flow cytometric panel for initial workup and residual disease evaluation of blastic plasmacytoid dendritic cell neoplasm. Haematologica, 2020, 105: 1-24

[90] KimMJ, NasrA, KabirB, et al.. Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm: A Systematic Literature Review. J Pediatr Hematol Oncol, 2017, 39(7): 528-537

[91] JegalianAG, BuxbaumNP, FacchettiF, et al.. Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications. Haematologica, 2010, 95(11): 1873-1879

[92] TsagarakisNJ, KentrouNA, PapadimitriouKA, et al.. Acute lymphoplasmacytoid dendritic cell (DC2) leukemia: results from the Hellenic Dendritic Cell Leukemia Study Group. Leuk Res, 2010, 34(4): 438-446

[93] LucioniM, NovaraF, FiandrinoG, et al.. Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion. Blood, 2011, 118(17): 4591-4594

[94] HashikawaK, NiinoD, YasumotoS, et al.. Clinicopathological features and prognostic significance of CXCL12 in blastic plasmacytoid dendritic cell neoplasm. J Am Acad Dermatol, 2012, 66(2): 278-291

[95] LaribiK, Baugier de MaterreA, SobhM, et al.. Blastic plasmacytoid dendritic cell neoplasms: results of an international survey on 398 adult patients. Blood Adv, 2020, 4(19): 4838-4848

[96] Kharfan-DabajaMA, ReljicT, MurthyHS, et al.. Allogeneic Hematopoietic Cell Transplantation Is an Effective Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm in First Complete Remission: Systematic Review and Meta-analysis. Clin Lymphoma Myeloma Leuk, 2018, 18(11): 703-709

[97] YunS, ChanO, KerrD, et al.. Survival outcomes in blastic plasmacytoid dendritic cell neoplasm by firstline treatment and stem cell transplant. Blood Adv, 2020, 4(14): 3435-3442

[98] PemmarajuN, LaneAA, SweetKL, et al.. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med, 2019, 380(17): 1628-1637

[99] JenEY, GaoX, LiL, et al.. FDA Approval Summary: Tagraxofusp-erzs For Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm. Clin Cancer Res, 2020, 26(3): 532-536

[100] AglianoA, Martin-PaduraI, MarighettiP, et al.. Therapeutic effect of lenalidomide in a novel xenograft mouse model of human blastic NK cell lymphoma/blastic plasmacytoid dendritic cell neoplasm. Clin Cancer Res, 2011, 17(19): 6163-6173

[101] PhilippeL, CeroiA, Bôle-RichardE, et al.. Bortezomib as a new therapeutic approach for blastic plasmacytoid dendritic cell neoplasm. Haematologica, 2017, 102(11): 1861-1868

[102] MarmousetV, JorisM, MerluscaL, et al.. The lenalidomide/bortezomib/dexamethasone regimen for the treatment of blastic plasmacytoid dendritic cell neoplasm. Hematol Oncol, 2019, 37(4): 487-489

[103] MonteroJ, StephanskyJ, CaiT, et al.. Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax. Cancer Discov, 2017, 7(2): 156-164

[104] GrushchakS, JoyC, GrayA, et al.. Novel treatment of blastic plasmacytoid dendritic cell neoplasm: A case report. Medicine (Baltimore), 2017, 96(51): e9452

[105] PicciniM, LoscoccoGG, GianfaldoniG, et al.. Quick complete response achievement with venetoclax and azacitidine in a case of relapsed disseminated blastic plasmacytoid dendritic cell neoplasm. Ann Hematol, 2020, 99(4): 907-909

[106] KovtunY, JonesGE, AdamsS, et al.. ACD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells. Blood Adv, 2018, 2(8): 848-858

[107] AngelovaE, AudetteC, KovtunY, et al.. CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia. Haematologica, 2019, 104(4): 749-755

[108] GillS, TasianSK, RuellaM, et al.. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood, 2014, 123(15): 2343-2354

[109] Bôle-RichardE, FredonM, BiichléS, et al.. CD28/4-1BB CD123 CAR T cells in blastic plasmacytoid dendritic cell neoplasm. Leukemia, 2020, 34(12): 3228-3241

[110] CeroiA, MassonD, RoggyA, et al.. LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis. Blood, 2016, 128(23): 2694-2707

[111] ShiY, WangE. Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic review. Arch Pathol Lab Med, 2014, 138(4): 564-569