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Functional heterogeneity exceeds genetic heterogeneity in chronic myelomonocytic leukemia

ABSTRACT: Functional heterogeneity exceeds genetic heterogeneity in chronic myelomonocytic leukemia

PROVIDER: PRJNA464355 | ENA |

REPOSITORIES: ENA

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Functional heterogeneity exceeds genetic heterogeneity in chronic myelomonocytic leukemia

Project description:The respective role of genetic and epigenetic heterogeneity in the functional diversity of cells that compose human malignancies remains poorly understood. This question is addressed in chronic myelomonocytic leukemia (CMML), a myeloid neoplasm in which clinical diversity contrasts with a limited genetic heterogeneity. By reprogramming CMML-patient and healthy donor CD34-positive cells, we generated induced pluripotent cell clones (iPSC). In one of the patients, we captured a part of the genetic heterogeneity of the leukemic clone and analyzed five iPSCs with two distinct genetic backgrounds, i.e. with and without KRASG12D mutation. Hematopoietic differentiation of these clones recapitulated the main features of the patient disease, including overproduction of granulomonocytes and dysmegakaryopoiesis. These analyses also disclosed significant discrepancies in the behavior as well as the DNA methylation pattern of hematopoietic cells derived from iPSCs with similar genetic background. Introduction of SRSF2P95H mutation in a KRAS-mutated iPSC partially suppressed the functional and epigenetic gap with the other KRAS-mutated clone. Despite the similar functional behavior of these two clones, only the SRSF2P95H clone responded to low doses of the hypomethylating agent decitabine by restoration of a more balanced production of hematopoietic cells. These analyses unravel additional levels of intraclonal heterogeneity beyond the coding mutations, which may also modulate individual cell response to treatment.

2020-04-14 | GSE114115 | GEO

Transcriptome of chronic myelomonocytic leukemia

Project description:We report the gene expression of human chronic myelomonocytic leukemia by performing whole transcriptome shotgun sequencing of peripheral blood mononuclear cells of patients with chronic myelomonocytic leukemia.

2020-08-14 | GSE156209 | GEO

Transcriptome of chronic myelomonocytic leukemia

Project description:Transcriptome of chronic myelomonocytic leukemia

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Transcriptome of ASXL1-mutant and ASXL1-wildtype chronic myelomonocytic leukemia

Project description:We report the gene expression of human chronic myelomonocytic leukemia by performing whole transcriptome shotgun sequencing of bone marrow mononuclear cells of patients with chronic myelomonocytic leukemia.

2022-02-21 | GSE159543 | GEO

Epigenome of ASXL1-mutant and ASXL1-wildtype chronic myelomonocytic leukemia

Project description:We report the chromatin characteristics of human chronic myelomonocytic leukemia by performing chromatin immunoprecipitation sequencing of histone modifications (ChIP-seq), immunoprecipitation sequencing of (hydroxy-)methylated residues (DIP-seq), and transposase accessibility sequencing (ATAC-seq) of bone marrow mononuclear cells of patients with chronic myelomonocytic leukemia.

2022-02-21 | GSE159886 | GEO

Methylation and chromatin abnormalities in chronic myelomonocytic leukemia.

Project description:In this study, institutional IRB approval was obtained and peripheral blood and bone marrow samples on patients with chronic myelomonocytic leukemia were collected. On the samples, we performed chromatin immuno-precipitation and next generation sequencing to assess histone modifications and epigenetic changes associated with proliferative and dysplastic phenotypes.

2020-08-18 | GSE156377 | GEO

RNA-sequencing of Chronic Myelomonocytic Leukemia and healthy donors bone marrow samples

Project description:RNA-seq of bone marrow samples of chronic myelomonocytic leukemia (CMML) patients and healthy donors to identify the molecular DNA repair pathways involved in CMML pathogenic

2020-08-07 | GSE102312 | GEO

Chronic myelomonocytic leukemia

Project description:Chronic myelomonocytic leukemia is an aggressive hematological malignancy with dismal outcomes, with the pCMML subtype in particular having median OS of <2 years and high rates of AML transformation (Patnaik et al., 2014). Given limited therapeutic options for affected patients, we carried out this study to define the genetic and epigenetic landscape of pCMML and identify therapies that could modify disease biology.

| EGAS00001005107 | EGA

Methylation and chromatin abnormalities in chronic myelomonocytic leukemia.

Project description:Methylation and chromatin abnormalities in chronic myelomonocytic leukemia.

| PRJNA657628 | ENA

Affymetrix SNP array data for chronic myelomonocytic leukemia samples

Project description:Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder with heterogeneous clinical, morphological and genetic characteristics. Clonal cytogenetic abnormalities are found in 20-30% of patients with CMML. Patients with low risk cytogenetic features (normal karyotype and isolated loss of Y chromosome) account for approximately 80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. SNP-A were performed in 82 CMML patients with low risk karyotypes and uninformative results for conventional G-banding cytogenetics (CC).

2015-12-01 | GSE67460 | GEO

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