Gene expression of blood cells in a patient with GATA2 deficiency.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA543412 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To determine the difference of GATA2 related gene expression in blood cells. Gene expression of GATA2 deficiency comparing to a healthy person.
2022-05-17 | GSE131372 | GEO
Project description:The majority (72%) of adolescents with myelodysplastic syndrome and monosomy 7 carry an underlying GATA2 deficiency. Nowadays, chemotherapy and allogenic hematopoietic stem cell transplantation (HSCT) are the only cure, pointing out the urgent need to develop reliable predictive tools. Familial cases carrying the same mutation in the GATA2 gene develop the disease at different age. The trigger of the disease is still unknown. Therefore, it is needed to understand the genetic mechanisms (mutations) and epigenetic mechanism, such as, DNA methylation, a cellular mechanism to control gene expression. Abnormal DNA methylation has been linked to several adverse outcomes, including human diseases. In this study, we deeply characterized 20 Spanish GATA2 deficient patients; study the presence of secondary mutations, clinical phenotype and DNA methylation. We have found that the most frequent secondary mutations are in STAG2 and ASXL1 genes, detected in 30% and 20% of the patients, respectively, a similar ratio has been described in a bigger cohort, showing that our 20-patient cohort is representative of the GATA2 deficiency scenario. For the first time, we found a specific hypermethylated signature in GATA2 patients, opening a novel point of view in the GATA2-patient diagnostic and facilitating the risk estimation of themselves. Furthermore, whether the methylation profiling is accurate enough, it will be useful to predict the onset of the disease progression.
2023-06-30 | E-MTAB-12551 | biostudies-arrayexpress
Project description:The majority (72%) of adolescents with myelodysplastic syndrome and monosomy 7 carry an underlying GATA2 deficiency. Nowadays, chemotherapy and allogenic hematopoietic stem cell transplantation (HSCT) are the only cure, pointing out the urgent need to develop reliable predictive tools. Familial cases carrying the same mutation in the GATA2 gene develop the disease at different age. The trigger of the disease is still unknown. Therefore, it is needed to understand the genetic mechanisms (mutations) and epigenetic mechanism, such as, DNA methylation, a cellular mechanism to control gene expression. Abnormal DNA methylation has been linked to several adverse outcomes, including human diseases. In this study, we deeply characterized 20 Spanish GATA2 deficient patients; study the presence of secondary mutations, clinical phenotype and DNA methylation. We have found that the most frequent secondary mutations are in STAG2 and ASXL1 genes, detected in 30% and 20% of the patients, respectively, a similar ratio has been described in a bigger cohort, showing that our 20-patient cohort is representative of the GATA2 deficiency scenario. For the first time, we found a specific hypermethylated signature in GATA2 patients, opening a novel point of view in the GATA2-patient diagnostic and facilitating the risk estimation of themselves. Furthermore, whether the methylation profiling is accurate enough, it will be useful to predict the onset of the disease progression.
2023-03-01 | GSE221745 | GEO
Project description:Typical features of GATA2 deficiency were observed in a individual with wild-type GATA2 sequence. The patient had a de novo tandem duplication of 187Kb spanning GATA2 and RPN1 containing a deletion of 25Kb 5’ of RPN1, inherited from the mother. The deletion is a copy number variant present in about 4% of Europeans (GRCh37: esv2725896 and nsv513733; GRCh38: esv3597711) and removes an alternative 5’ start site of RPN1 at 128,400Kb, associated with CTCF and H3K27ac binding peaks. A second copy of GATA2 is translocated to this region by the tandem duplication. RNA-Seq was underatken in order to identify any gene fussion events resulting from the mutation and to inverstigate differences in gene expression between the patient and controls.
2021-05-10 | GSE166201 | GEO
Project description:GATA2 Deficiency and the MonoMAC Syndrome
| PRJNA955837 | ENA
Project description:GATA2 Deficiency and the MonoMAC Syndrome
| PRJNA955848 | ENA
Project description:GATA2 deficiency is an autosomal dominant germline disorder of immune dysfunction and bone marrow failure with a high propensity for leukemic transformation in adolescents, present in up to 7% of pediatric myelodysplastic syndrome (MDS) and 15% of advanced MDS cases. While sequencing studies have identified several secondary mutations thought to contribute to malignancy, the mechanisms of disease progression have been difficult to identify due to a lack of disease-specific experimental models. Here, we generated a murine model of one of the most common GATA2 mutations associated with leukemic progression in GATA2 deficiency, Gata2R396Q/+. While mutant mice exhibit mild defects in peripheral blood output throughout life, they display significant hematopoietic abnormalities in the bone marrow (BM), including a reduction in hematopoietic stem cell (HSC) function and intrinsic biases toward specific stem cell subsets that differ from previous models of GATA2 loss. Supporting this observation, single-cell RNA sequencing of BM hematopoietic progenitors revealed a loss of HSC stemness, myeloid-bias, and accelerated ageing phenotype. Importantly, we show that Gata2R396Q/+ exerts effects early in hematopoietic development, as mutant mice generate fewer HSCs in the aorta gonad mesonephros, and fetal liver HSCs have reduced function. This reduced pool of HSCs and aged phenotype could be potential contributors to leukemic transformation in patients, and our model provides a useful tool to study the mechanisms of malignant transformation in GATA2 deficiency.
2024-12-23 | GSE275213 | GEO
Project description:Patients with GATA2 deficiency are predisposed to developing myelodysplastic syndrome (MDS), which can progress to acute myeloid leukemia (AML). This progression is often associated with the acquisition of additional cytogenetic and somatic alterations. Mutations in SETBP1 and ASXL1 genes are recurrently observed in GATA2 patients, but their precise roles in disease progression remain poorly understood. Here we developed a hiPSC-based system to investigate the functional impact of SETBP1 and ASXL1 mutations in the context of germline GATA2 haploinsufficiency. Using precise genome editing, we recreated patient-relevant combinations of these mutations to model distinct premalignant stages of GATA2 deficiency. We demonstrate that heterozygous GATA2 mutation alone has a limited impact on early hematopoietic progenitors, without disrupting myeloid differentiation. In contrast, acquisition of SETBP1 or ASXL1 mutations impairs hematopoietic differentiation in a GATA2 deficient background, leading to a premalignant state marked by reduced myeloid progenitor output. Strikingly, the combination of all three mutations results in a severe depletion of myeloid progenitors, closely recapitulating hematopoietic defects observed in GATA2-related MDS and highlighting a synergistic interplay among the mutations. We provide new insights into the molecular mechanism underlying GATA2 deficiency progression, revealing that SETBP1 mutation plays a dominant role in establishing a stable chromatin accessibility landscape, even when co-occurring with ASXL1. Our study establishes a novel humanized model system for studying GATA2 deficiency. This model provides new insights into the cellular and molecular events underlying the progression of myeloid impairment in GATA2 deficiency and represents a platform for testing future therapeutic strategies.
2025-10-02 | GSE265824 | GEO