HAEM5:Blastic plasmacytoid dendritic cell neoplasm: Difference between revisions

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Hao Liu, MD and Daynna J. Wolff, PhD

==WHO Classification of Disease==

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|Acceptable

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|Not Recommended

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A recurrent balanced translocation t(6;8)(p21;q24) involving the ''MYC'' locus was exclusively identified in BPDCN<ref name=":4">{{Cite journal|last=Kubota|first=Sho|last2=Tokunaga|first2=Kenji|last3=Umezu|first3=Tomohiro|last4=Yokomizo-Nakano|first4=Takako|last5=Sun|first5=Yuqi|last6=Oshima|first6=Motohiko|last7=Tan|first7=Kar Tong|last8=Yang|first8=Henry|last9=Kanai|first9=Akinori|date=2019|title=Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm|url=https://www.ncbi.nlm.nih.gov/pubmed/30971697|journal=Nature Communications|volume=10|issue=1|pages=1653|doi=10.1038/s41467-019-09710-z|issn=2041-1723|pmc=6458132|pmid=30971697}}</ref><ref name=":5">{{Cite journal|last=Sumarriva Lezama|first=Lhara|last2=Chisholm|first2=Karen M.|last3=Carneal|first3=Eugene|last4=Nagy|first4=Alexandra|last5=Cascio|first5=Michael J.|last6=Yan|first6=Jie|last7=Chang|first7=Chung-Che|last8=Cherry|first8=Athena|last9=George|first9=Tracy I.|date=2018|title=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|url=https://www.ncbi.nlm.nih.gov/pubmed/29884995|journal=Histopathology|volume=73|issue=5|pages=767–776|doi=10.1111/his.13668|issn=1365-2559|pmid=29884995}}</ref><ref name=":6">{{Cite journal|last=Nakamura|first=Y.|last2=Kayano|first2=H.|last3=Kakegawa|first3=E.|last4=Miyazaki|first4=H.|last5=Nagai|first5=T.|last6=Uchida|first6=Y.|last7=Ito|first7=Y.|last8=Wakimoto|first8=N.|last9=Mori|first9=S.|date=2015|title=Identification of SUPT3H as a novel 8q24/MYC partner in blastic plasmacytoid dendritic cell neoplasm with t(6;8)(p21;q24) translocation|url=https://www.ncbi.nlm.nih.gov/pubmed/25860292|journal=Blood Cancer Journal|volume=5|pages=e301|doi=10.1038/bcj.2015.26|issn=2044-5385|pmc=4450326|pmid=25860292}}</ref><ref name=":7">{{Cite journal|last=Sakamoto|first=Kana|last2=Katayama|first2=Ryohei|last3=Asaka|first3=Reimi|last4=Sakata|first4=Seiji|last5=Baba|first5=Satoko|last6=Nakasone|first6=Hideki|last7=Koike|first7=Sumie|last8=Tsuyama|first8=Naoko|last9=Dobashi|first9=Akito|date=2018|title=Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response|url=https://www.ncbi.nlm.nih.gov/pubmed/29795241|journal=Leukemia|volume=32|issue=12|pages=2590–2603|doi=10.1038/s41375-018-0154-5|issn=1476-5551|pmid=29795241}}</ref><ref name=":8">{{Cite journal|last=Boddu|first=Prajwal C.|last2=Wang|first2=Sa A.|last3=Pemmaraju|first3=Naveen|last4=Tang|first4=Zhenya|last5=Hu|first5=Shimin|last6=Li|first6=Shaoying|last7=Xu|first7=Jie|last8=Medeiros|first8=L. Jeffrey|last9=Tang|first9=Guilin|date=2018|title=8q24/MYC rearrangement is a recurrent cytogenetic abnormality in blastic plasmacytoid dendritic cell neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/29407586|journal=Leukemia Research|volume=66|pages=73–78|doi=10.1016/j.leukres.2018.01.013|issn=1873-5835|pmid=29407586}}</ref>. The prevalence of ''MYC'' translocation in BPDCN is 5% -12%<ref name=":5" />. Rearrangements involving the ''MYC'' locus on 8q24 are associated with MYC protein overexpression and specific clinical features, including older onset age and shorter median survival<ref name=":5" />. ''RUNX2'', located on chromosome 6p21, is strongly expressed in pDCs and BPDCN cells. The t(6,8) generates mutant-allele super-enhancer of ''RUNX2'' which may increase the expression of MYC and lead to the development of BPDCN<ref name=":4" />. SUPT3H, a TATA-binding protein-associated factors (TAF)-associated protein, was identified as a novel 8q24/''MYC'' partner in BPDCN<ref name=":6" />.

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

* Gene Mutations (SNV/INDEL)}}</blockquote>

*Age is an adverse impact factor for prognosis<ref name=":0" />.

*A new targeted therapy, Tagraxofusp (SL-401, ELZONRIS) was recently approved.  This agent is a CD123-directed cytotoxin consisting of recombinant human interleukin-3 fused to a truncated diphtheria toxin<ref name=":1" /><ref name=":3" /><ref name=":12" />.

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|<span class="blue-text">EXAMPLE:</span>

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1).Deletion of the 9p21.3 locus<ref name=":10">{{Cite journal|last=Lezama|first=Lhara|last2=Ohgami|first2=Robert S.|date=2019|title=Expounding on the essence of epigenetic and genetic abnormalities in blastic plasmacytoid dendritic cell neoplasms|url=https://www.ncbi.nlm.nih.gov/pubmed/30930334|journal=Haematologica|volume=104|issue=4|pages=642–643|doi=10.3324/haematol.2018.211557|issn=1592-8721|pmc=6442968|pmid=30930334}}</ref>:

!Chromosomal Pattern

!Molecular Pathogenesis

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|<span class="blue-text">EXAMPLE:</span>

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*Chromosomal abnormalities are identified in the majority of BPDCN cases; about two thirds of BPDCN patients have an abnormal karyotype<ref name=":0" />.

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|<span class="blue-text">EXAMPLE:</span>''EGFR''

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

*Common gene mutations in BPDCN: ''TET2'', ''ASXL1, NRAS, ATM'', and ''NPM1''<ref name=":0" /><ref name=":2" /><ref name=":5" /><ref name=":11">{{Cite journal|last=Sapienza|first=Maria Rosaria|last2=Abate|first2=Francesco|last3=Melle|first3=Federica|last4=Orecchioni|first4=Stefania|last5=Fuligni|first5=Fabio|last6=Etebari|first6=Maryam|last7=Tabanelli|first7=Valentina|last8=Laginestra|first8=Maria Antonella|last9=Pileri|first9=Alessandro|date=2019|title=Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target|url=https://www.ncbi.nlm.nih.gov/pubmed/30381297|journal=Haematologica|volume=104|issue=4|pages=729–737|doi=10.3324/haematol.2018.202093|issn=1592-8721|pmc=6442957|pmid=30381297}}</ref>.

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·        BCL-2 and NF-ĸB pathways<ref name=":10" /><ref>{{Cite journal|last=Chang|first=Kung-Chao|last2=Yu-Yun Lee|first2=Julia|last3=Sakamoto|first3=Kana|last4=Baba|first4=Satoko|last5=Takeuchi|first5=Kengo|date=2019|title=Blastic plasmacytoid dendritic cell neoplasm with immunoblastoid morphology and MYC rearrangement and overexpression|url=https://www.ncbi.nlm.nih.gov/pubmed/30482401|journal=Pathology|volume=51|issue=1|pages=100–102|doi=10.1016/j.pathol.2018.09.058|issn=1465-3931|pmid=30482401}}</ref>

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==Notes==

          

<nowiki>*</nowiki>''Citation of this Page'': “Blastic plasmacytoid dendritic cell neoplasm”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Blastic_plasmacytoid_dendritic_cell_neoplasm</nowiki>.