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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:
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 or SL-401 in Combination with Azacitidine in Patients
with High-Risk Myelodysplastic Syndrome (MDS)
18-013: A Phase 1/2, Multi-center, Open-label Study of IMGN632 Monotherapy Administered Intravenously in Patients with CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies
18-045: A Phase 1 Study of Venetoclax, a BCL2 Antagonist, for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
19-544: A Phase 1/2, Open Label, Multicenter Trial to Assess the Safety and Efficacy of MB-102 in Patients with Relapsed or Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm, Acute Myeloid Leukemia, and High Risk Myelodysplastic Syndrome
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.
Andrew Lane, MD, PhD, highlights the male-biased spliceosome mutations in blastic plasmacytoid dendritic cell neoplasm as presented at ASH 2020.
Andrew Lane, MD, PhD, Shares Updates on Treating BPDCNDr. Lane recaps the promising results presented at the ASH 2017 Annual Meeting from a phase 2 trial of SL-401 for blastic plasmacytoid dendritic cell neoplasm (BPDCN), as well as results from his lab exploring why some patients respond to SL-401 and others do not.
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