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Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response (CAL1 vs PMDC05)

ABSTRACT: Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response (CAL1 vs PMDC05)

PROVIDER: PRJNA445269 | ENA |

REPOSITORIES: ENA

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Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response

Project description:Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response

| PRJNA445271 | ENA

Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response (CAL1 vs PMDC05)

Project description:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYC-BPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYC-BPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYC-BPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extraterminal protein (BETis) and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYC-BPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN in accordance with precision medicine.

2018-05-29 | GSE112209 | GEO

Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response (CAL-1, JQ1 treatment)

2018-05-29 | GSE112210 | GEO

Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response (CAL-1, JQ1 treatment)

Project description:Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response (CAL-1, JQ1 treatment)

| PRJNA445273 | ENA

Recurrent 8q24 rearrangement in BPDCN: association with immunoblastoid cytomorphology, MYC expression, and drug response

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-05-29 | GSE112211 | GEO

RUNX2 promotes the development of Blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Project description:To understand how RUNX2 promoted the development of BPDCN, we transduced RUNX2-directed shRNA vectors in a BPDCN cell line, CAL-1 and performed microarray analysis of RUNX2-knocked down CAL-1 cells

2018-02-06 | GSE110140 | GEO

Expression data from 12 BPDCN samples, 35 T-ALL samples, and 65 AML samples

Project description:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological. We used transcriptomic analysis to investigate LXR pathway, and cholesterol metabolism in leukemic cells. Malignancy with a poor prognosis that derives from plasmacytoid dendritic cells (PDC). No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared to those of acute myeloid leukemia (AML) and T-acute lymphoblastic leukemia (T-ALL), as well as the transcriptomic signature of primary PDC. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell lines restored LXR target gene expression and increased cholesterol efflux via the upregulation of ATP Binding Cassette (ABC) transporters, ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell proliferation and inducing intrinsic apoptotic cell death. LXR activation in BPDCN cells was shown to interfere with three signaling pathways associated with leukemic cell survival, namely: NF-κB activation, as well as Akt and STAT5 phosphorylation in response to the BPDCN growth/survival factor IL-3. These effects were increased by the stimulation of cholesterol efflux through a lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN-induced cytopenia associated with an increased survival after LXR agonist treatment. This demonstrates that cholesterol homeostasis is modified in BPDCN and can be normalized by treatment with LXR agonists which can be proposed as a new therapeutic approach.

2017-02-10 | GSE89565 | GEO

BPDCN MYB Fusions Regulate Cell Cycle Genes, Impair Differentiation and Induce Myeloid-Dendritic Cell Leukemia [HoxRNASeq]

Project description:MYB fusions are recurrently found in select cancers, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), an acute leukemia with poor prognosis. They are markedly enriched in BPDCN compared to other blood cancers, and in some patients are the only obvious somatic mutation detected. This suggests they may alone be sufficient to drive dendritic cell transformation. MYB fusions are hypothesized to alter the normal transcription factor activity of MYB, but mechanistically how they promote leukemogenesis is poorly understood. Using CUT&RUN chromatin profiling, we found that in BPDCN leukemogenesis, MYB switches from being a regulator of dendritic cell lineage genes to aberrantly regulating G2/M cell cycle control genes. MYB fusions found in BPDCN patients increased the magnitude of DNA binding at these locations, and this was linked to BPDCN-associated gene expression changes. Furthermore, expression of MYB fusions in vivo impaired dendritic cell differentiation and induced transformation to generate a mouse model of myeloid-dendritic acute leukemia. Therapeutically, we present evidence that all-trans retinoic acid (ATRA) may cause loss of MYB protein and cell death in BPDCN.

2024-11-15 | GSE261767 | GEO

BPDCN MYB Fusions Regulate Cell Cycle Genes, Impair Differentiation and Induce Myeloid-Dendritic Cell Leukemia [HoxCutRun]

2024-11-15 | GSE261666 | GEO

BPDCN MYB Fusions Regulate Cell Cycle Genes, Impair Differentiation and Induce Myeloid-Dendritic Cell Leukemia [BPDCNCutRun]

2024-11-15 | GSE261534 | GEO