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Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159512 | GEO | 2020/10/22

REPOSITORIES: GEO

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Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Nanopore]

Project description:Resistance to chemotherapy is the most common cause of treatment failure in acute myeloid leukemia and the drug efflux pump ABCB1 is a critical mediator. Here we demonstrate that in vitro daunorubicin exposure can induce activating ABCB1 promoter translocations in human myeloid cells, similar to those recently described in recurrent high-grade serous ovarian and breast cancer. We then develop a targeted nanopore sequencing approach that enables efficient identification of ABCB1 structural variants in high-grade serous ovarian cancer. Finally, we confirm that ABCB1high cases of relapsed AML are not characterized by ABCB1 promoter translocations but instead show high-level activity of native promoters, consistent with endogenous regulation.

2020-10-22 | GSE159324 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Targeted Resequencing]

2020-10-22 | GSE159331 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [RNAseq]

2020-10-22 | GSE159391 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [ChIP-seq]

2020-10-22 | GSE159317 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [4C-seq]

2020-10-22 | GSE159394 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Nanopore]

Project description:Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Nanopore]

| PRJNA668367 | ENA

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia

Project description:Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia

| PRJNA669673 | ENA

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in cancer.

Project description:BackgroundResistance to chemotherapy is the most common cause of treatment failure in acute myeloid leukemia (AML) and the drug efflux pump ABCB1 is a critical mediator. Recent studies have identified promoter translocations as common drivers of high ABCB1 expression in recurrent, chemotherapy-treated high-grade serous ovarian cancer (HGSC) and breast cancer. These fusions place ABCB1 under the control of a strong promoter while leaving its open reading frame intact. The mechanisms controlling high ABCB1 expression in AML are largely unknown. We therefore established an experimental system and analysis pipeline to determine whether promoter translocations account for high ABCB1 expression in cases of relapsed human AML.MethodsThe human AML cell line THP-1 was used to create a model of chemotherapy resistance in which ABCB1 expression was driven by a promoter fusion. The THP-1 model was used to establish a targeted nanopore long-read sequencing approach that was then applied to cases of ABCB1high HGSC and AML. H3K27Ac ChIP sequencing was used to assess the activity of native promoters in cases of ABCB1high AML.ResultsProlonged in vitro daunorubicin exposure induced activating ABCB1 promoter translocations in human THP-1 AML cells, similar to those recently described in recurrent high-grade serous ovarian and breast cancers. Targeted nanopore sequencing proved an efficient method for identifying ABCB1 structural variants in THP-1 AML cells and HGSC; the promoter translocations identified in HGSC were both previously described and novel. In contrast, activating ABCB1 promoter translocations were not identified in ABCB1high AML; instead H3K27Ac ChIP sequencing demonstrated active native promoters in all cases studied.ConclusionsDespite frequent high level expression of ABCB1 in relapsed primary AML we found no evidence of ABCB1 translocations and instead confirmed high-level activity of native ABCB1 promoters, consistent with endogenous regulation.

| S-EPMC7654162 | biostudies-literature

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Targeted Resequencing]

Project description:Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Targeted Resequencing]

| PRJNA668379 | ENA

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [RNAseq]

Project description:Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [RNAseq]

| PRJNA668756 | ENA

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