Exploration of Targeted Anti-tumor Therapy

Table 1. Recurrent genomic and cytogenetic alterations in blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Gene/Abnormality	Locus	Type of alteration	Mutation frequency (%)	Key biological function	References
Tet methylcytosine dioxygenase 2 (TET2)	4q24	Missense, frameshift, nonsense mutation	57	Epigenetic regulation (DNA demethylation)	[1]
Additional sex combs like 1 (ASXL1)	20p11	Frameshift, nonsense mutation	33	Epigenetic regulation (histone modification)	[1]
IDH2 (isocitrate dehydrogenase 2)	15q26.1	Point mutation	Rare, but present	Epigenetic regulation (isocitrate metabolism)	[2]
Transcription factor 4(TCF4)	18q21.2	Overexpression	Common	TCF (oncogenic master regulator)	[21]
Interleukin-3 receptor alpha chain (CD123) (IL3RA)	Xp11.3/Yp11.3	Overexpression	Universally high	Interleukin-3 receptor, therapeutic target	[8]
Chromosome 5q	5q31–q33	Deletion	Recurrent	Unknown, linked to other myeloid neoplasms	[2]
CDKN2A/B (cyclin-dependent kinase inhibitor 2A/2B)	9p21	Deletion (p21)	Common	Unknown, associated with worse prognosis	[2]
MYC	8q24.21	Rearrangement	Common	TCFs, cell cycle control	[15]
MYB	6q23.3	Rearrangement	Common	TCFs, cell cycle control	[15]
RB1 (retinoblastoma 1)	13q14.2	Loss-of-function alterations: truncating mutations with loss of heterozygosity (LOH) at the RB1 locus, and broader 13q14 deletions	Uncommon	Tumor suppressor controlling Gap 1 to synthesis phase (cell cycle transition) (G1–S) cellcycle transition	[26]
IKZF1 (IKAROS family zinc finger 1)	7p12.2	Predominantly focal interstitial deletions and unbalanced rearrangements at 7p12.2 causing loss of function	Common	TCF essential for plasmacytoid dendritic cell (pDC) precursor differentiation	[27]

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Acknowledgments

During the preparation of this work, the author(s) used an AI-based tool (Gemini) for figure generation. After using this tool, the author(s) reviewed and edited the content as needed in Canva and PowerPoint and take full responsibility for the content of the publication.

Author contributions

PPP: Conceptualization, Investigation, Writing—original draft, Supervision, Funding acquisition, Writing—review & editing. ML, LC: Investigation, Validation, Writing—original draft, Writing—review & editing. VT, PC, IL: Investigation, Validation. All authors read and approved the submitted version.

Conflicts of interest

Pier Paolo Piccaluga, who is the Editorial Board Member and Guest Editor of Exploration of Targeted Anti-tumor Therapy, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

The datasets supporting the findings of this study are available from the corresponding author upon reasonable request.

Funding

This work was supported by the Italian Ministry of Health (RC-2024-2790173), and PRIN 2022NXK38S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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