Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Center

Our team is focused on basic and clinical research to better understand BPDCN and improve outcomes. Recent research done at Dana-Farber and collaborating institutions has helped better understand BPDCN and has identified new molecular targets for new therapies for BPDCN. Findings include:

• All BPDCN cells overexpress CD123 (interleukin-3 receptor), a cell-surface protein. The BPDCN Center is one of the leaders of a national clinical trial of the targeted immunotoxin tagraxofusp (also known as Elzonris or SL-401), a novel agent that targets the IL-3 receptor (CD123). This led to approval of tagraxofusp as the first drug specifically approved for BPDCN.
• In the laboratory, we have learned how BPDCN becomes resistant to tagraxofusp. This led to a new clinical trial testing the combination of tagraxofusp with azacitidine, a therapy already used in patients with other types of leukemia.
• By studying the characteristics of patients' BPDCN and the treatment received, we have defined factors associated with survival and identified new chemotherapy and targeted therapies that might be active in the disease.

Featured Clinical Trials for BPDCN

17-056: Phase 1 Study of SL-401 in Combination with Azacitidine and Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia (AML) and in Treatment-Naive Subjects with AML Not Eligible for Standard Induction and in Subjects with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) or SL-401 in Combination with Azacitidine in Patients with High-Risk Myelodysplastic Syndrome (MDS)

18-013: Study of IMGN632 in Patients with Untreated BPDCN and Relapsed/Refractory BPDCN

Studying the Genomics of BPDCN

The research lab of Andrew Lane, MD, PhD, is also studying the genomics of BPDCN and modeling how specific somatic alterations (such as mutations in the DNA of BPDCN cells) contribute to dendritic cell transformation. Researchers recently discovered that BPDCN is highly and uniquely dependent on the BCL-2 protein for survival. BCL-2 is a "pro-survival" protein that enables cancer cells to escape the "pro-death" signals that normally command abnormal cells to self-destruct through apoptosis, a natural quality-control process in the body. Further, researchers confirmed that BPDCN is very sensitive to venetoclax, a BCL2 inhibitor developed at Dana-Farber. Two patients in a pilot study with relapsed disease responded to venetoclax. A clinical trial is currently underway to evaluate venetoclax in BPDCN patients. This research was reported in Cancer Discovery.

Lane’s lab research also led to the discovery that the reason why BPDCN is more common in males than females (~4:1 ratio) may be related to specific mutations on the X chromosome associated with the disease.