Transcriptome and methylation analysis of JMML patients compare to healthy prenatal and postnatal samples.
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PROVIDER: PRJNA817424 | ENA |
REPOSITORIES: ENA
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Project description:JMML (Juvenile myelomonocytic leukaemia) is a leukaemia hat only develops in young children and is thought to have a prenatal initiation. To study the relationship between JMML and normal ontogeny we studied the transcriptome of HSPC (hematopoietic stem and progenitor cells) sorted from sporadic JMML patients, healthy prenatal samples and from healthy age matched donors. Bulk transcriptome of sorted HSPC reveals that some JMML samples cluster with prenatal samples whereas other from a distinct cluster apart from any healthy samples. Methylation profile on bulk mononucleated cell on theses JMML patients, 2 healthy postnatal and 2 healthy prenatal samples is also investigated. The results show a global hypermethylation in JMML samples compared to healthy samples and a specific JMML group with a hypermethylated profile compared to all JMML samples.
2022-12-31 | GSE198919 | GEO
Project description:JMML (Juvenile myelomonocytic leukaemia) is a leukaemia that only develops in young children and is thought to have a prenatal initiation. To study the relationship between JMML and normal ontogeny we studied the transcriptome of HPC (hematopoietic progenitor cells) sorted from sporadic JMML patients, healthy prenatal samples and from healthy age matched donors. Bulk transcriptome of sorted HPC reveals that some JMML samples cluster with prenatal samples whereas other from a distinct cluster apart from any healthy samples.
2024-05-16 | GSE267628 | GEO
Project description:Transcriptome analysis of JMML patients compare to healthy prenatal and postnatal samples.
| PRJNA1112163 | ENA
Project description:Juvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. Interestingly, LIN28B overexpression was significantly correlated with higher HbF levels whereas patients with -7 seldom showed enhanced LIN28B expression. In line with LIN28B’s role as mediator of fetal hematopoiesis, this explains the biology behind the observation that patients with -7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Finally, high LIN28B expression was associated with poor clinical outcome in our JMML patient series, but not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified LIN28B as a crucial molecular player at the heart of a novel fetal-like subgroup in JMML.
2015-12-23 | GSE71452 | GEO
Project description:Juvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. Interestingly, LIN28B overexpression was significantly correlated with higher HbF levels whereas patients with -7 seldom showed enhanced LIN28B expression. In line with LIN28B’s role as mediator of fetal hematopoiesis, this explains the biology behind the observation that patients with -7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Finally, high LIN28B expression was associated with poor clinical outcome in our JMML patient series, but not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified LIN28B as a crucial molecular player at the heart of a novel fetal-like subgroup in JMML.
2015-12-23 | GSE71935 | GEO
Project description:Juvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. Interestingly, LIN28B overexpression was significantly correlated with higher HbF levels whereas patients with -7 seldom showed enhanced LIN28B expression. In line with LIN28B’s role as mediator of fetal hematopoiesis, this explains the biology behind the observation that patients with -7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Finally, high LIN28B expression was associated with poor clinical outcome in our JMML patient series, but not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified LIN28B as a crucial molecular player at the heart of a novel fetal-like subgroup in JMML.
2015-12-23 | GSE71449 | GEO
Project description:Juvenile myelomonocytic leukemia (JMML) is an aggressive cancer of young children initiated by mutations in NRAS, KRAS and other genes encoding proteins that modulate Ras signal output. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment and patients with relapsed and refractory disease have dismal outcomes. This trial evaluated the safety and efficacy of trametinib in advanced JMML. Kinase enrichment proteomic analysis was performed using available patient samples pre- or post-treatment with trametinib (NCT03190915) to evaluate the effects on the functional kinome.
2024-04-23 | PXD042328 | Pride
Project description:Juvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. Interestingly, LIN28B overexpression was significantly correlated with higher HbF levels whereas patients with -7 seldom showed enhanced LIN28B expression. In line with LIN28Bâ??s role as mediator of fetal hematopoiesis, this explains the biology behind the observation that patients with -7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Finally, high LIN28B expression was associated with poor clinical outcome in our JMML patient series, but not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified LIN28B as a crucial molecular player at the heart of a novel fetal-like subgroup in JMML. Gene expression was measured on Affymetrix in 38 JMML patients and 9 healthy donors in a validation cohort.
2015-12-23 | E-GEOD-71935 | biostudies-arrayexpress
Project description:Juvenile myelomonocytic leukemia (JMML) is a very rare and aggressive stem cell disease that mainly occurs in young children. RAS activation constitutes the core component of oncogenic signaling. In addition, the leukemic blasts of a quarter of JMML patients present with monosomy 7 (-7), whereas more than half of the patients show enhanced age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care. This results in an event-free survival of 50 - 60%, indicating that novel molecular driven therapeutic options are urgently needed. Using gene expression profiling in an extensive series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. Interestingly, LIN28B overexpression was significantly correlated with higher HbF levels whereas patients with -7 seldom showed enhanced LIN28B expression. In line with LIN28Bâ??s role as mediator of fetal hematopoiesis, this explains the biology behind the observation that patients with -7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Finally, high LIN28B expression was associated with poor clinical outcome in our JMML patient series, but not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified LIN28B as a crucial molecular player at the heart of a novel fetal-like subgroup in JMML. Gene expression was measured on Agilent in 44 JMML patients and 7 healthy donors in the discovery cohort. A validation cohort of 38 patients and 9 healthy donors was measured on Affymetrix. All patient data can be found in Supplementary Table S1.
2015-12-23 | E-GEOD-71449 | biostudies-arrayexpress
Project description:Activating mutations in PTPN11 gene are the most frequent in JMML patients. Here we explore the transcriptome of HSPC (hematopoietic stem and progenitor cells) sorted from sporadic JMML patients with PTPN11 mutation and from healthy age matched donnors. Bulk transcriptome of sorted HSPC reveals an inflammatory gene expression signature which may represent a future target for JMML therapy.
2021-09-06 | GSE183252 | GEO