Project description:Classification of acute lymphoblastic and myeloid leukemias (ALL and AML) remains heavily based on phenotypic resemblance to normal hematopoietic precursors. This framework can provide diagnostic challenges for immunophenotypically heterogeneous immature leukemias, and ignores recent advances in understanding of developmental multipotency of diverse normal hematopoietic progenitor populations that are identified by transcriptional signatures. We performed transcriptional analyses of a large series of acute myeloid and lymphoid leukemias and detected significant overlap in gene expression between cases in different diagnostic categories. Bioinformatic classification of leukemias along a continuum of hematopoietic differentiation identified leukemias at the myeloid/T-lymphoid interface, which shared gene expression programs with a series of multi or oligopotent hematopoietic progenitor populations, including the most immature CD34+CD1a-CD7- subset of early thymic precursors. Within these interface acute leukemias (IALs), transcriptional resemblance to early lymphoid progenitor populations and biphenotypic leukemias was more evident in cases originally diagnosed as AML, rather than T-ALL. Further prognostic analyses revealed that expression of IAL transcriptional programs significantly correlated with poor outcome in independent AML patient cohorts. Our results suggest that traditional binary approaches to acute leukemia categorization are reductive, and that identification of IALs could allow better treatment allocation and evaluation of therapeutic options.
Project description:We investigated DNA methylomes of 227 pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. The current study identified a link between DNA methylome of B-cell acute lymphoblastic leukemias (B-ALLs) and embryonic stem cell (ESC) bivalency, through which tumor cells can mimic the pluripotency of ESCs.
Project description:We investigated DNA methylomes of 227 pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. The current study identified a link between DNA methylome of B-cell acute lymphoblastic leukemias (B-ALLs) and embryonic stem cell (ESC) bivalency, through which tumor cells can mimic the pluripotency of ESCs.
Project description:We investigated DNA methylomes of 227 pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. The current study identified a link between DNA methylome of B-cell acute lymphoblastic leukemias (B-ALLs) and embryonic stem cell (ESC) bivalency, through which tumor cells can mimic the pluripotency of ESCs.
Project description:CEBPA/PU.1/TCF7 ChIP-seq of 6 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Low-coverage whole genome sequencing (ChIP input) of the same samples is also included as a control to be used in peak calling.
Project description:CTCF ChIP-seq of 39 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011059 (dataset).
Project description:Diagnostic classification of Acute Myeloid and Lymphoid Leukemias (AMLs and ALLs) is mostly based on immunophenotype. This approach can pose challenges for phenotypically heterogeneous immature leukemias, and doesn't take account of recent advances in understanding of the developmental multipotency of diverse hematopoietic progenitor populations. We performed transcriptional analyses of a large series of primary ALs, including a high proportion of immature cases, in order to understand the spectrum of differentation arrest in AL. These transcriptional profiles were compared with both normal hematopoietic progenitors and independent leukemia data-sets.
Project description:Hi-C of 17 primary samples obtained from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). As healthy controls, Hi-C of CD34+ HSPCs from 3 healthy donors were used. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011051 (dataset).
Project description:H3K27ac ChIP-seq of 79 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). In addition, 4 samples derived from CD34+ cord blood cells of healthy donors were included. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011060 (dataset).