Publications by authors named "Giraudier S"
Despite the advances in the understanding and treatment of myeloproliferative neoplasm (MPN), the disease remains incurable with the risk of evolution to acute myeloid leukemia or myelofibrosis (MF). Unfortunately, the evolution of the disease to MF remains poorly understood, impeding preventive and therapeutic options. Recent studies in solid tumor microenvironment and organ fibrosis have shed instrumental insights on their respective pathogenesis and drug resistance, yet such precise data are lacking in MPN.
View Article and Find Full Text PDFMyeloproliferative neoplasms (MPNs) are characterized by an increased production of blood cells due to the acquisition of mutations such as JAK2. TGF-β, whose secretion is increased in MPN patients, is known to negatively regulate haematopoietic stem cell (HSC) proliferation. Using an isogenic JAK2 or JAK2 wild-type UT-7 cell line we observed that JAK2 cells resist to TGF-β antiproliferative activity.
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- The study compares the clinical characteristics of primary myelofibrosis (PMF) and secondary myelofibrosis (SMF), highlighting key differences in patient presentation and symptoms.
- It explores the molecular landscape of both conditions, analyzing genetic mutations and other molecular factors that may influence the disease.
- The research also focuses on prognosis scoring systems, assessing how well they predict outcomes and survival rates for patients with PMF and SMF.
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- Classical myeloproliferative neoplasms (MPNs) involve the excessive growth of myeloid cells and can progress to conditions like myelofibrosis or acute myeloid leukemia (AML), with TP53 mutations linked to AML in MPN patients.
- A study using a mouse model showed that JAK2V617F/Vav-Cre/Trp53 mice had similar traits to JAK2V617F/Vav-Cre mice, but their growth was less competitive when mixed.
- RNA sequencing indicated that many genes regulated by JAK2V617F were also influenced by the absence of p53, especially regarding resistance to treatments like interferon-α, suggesting that while TP53 is
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- Current risk scores for thrombotic events in myeloproliferative neoplasms (MPN) fail to differentiate between arterial and venous thrombosis, even though they have different causes and implications.
- A new score called ARTS, which considers factors like prior arterial thrombosis, age over 60, cardiovascular issues, and specific gene mutations, effectively stratifies patients into low- and high-risk groups for arterial thrombosis.
- Conversely, the VEnous Thrombosis Score (VETS), which only looks at prior venous thrombosis and JAK2 mutations, does not perform well, highlighting the need for better venous risk assessments that address its complexity.
Heterozygous mutation targeting proline 95 in Serine/Arginine-rich Splicing Factor 2 (SRSF2) is associated with V617F mutation in Janus Activated Kinase 2 (JAK2) in some myeloproliferative neoplasms (MPNs), most commonly primary myelofibrosis. To explore the interaction of Srsf2 with Jak2, we generated Cre-inducible knock-in mice expressing these mutants under control of the stem cell leukemia (Scl) gene promoter. In transplantation experiments, Srsf2 unexpectedly delayed myelofibrosis induced by Jak2 and decreased TGFβ1 serum level.
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- * These conditions typically begin with a chronic phase and can change to more aggressive forms like myelofibrosis or acute leukemia over time.
- * Recent advancements in research techniques allow for a deeper understanding of how mutations develop and interact within individual cells, shedding light on disease progression and complexity.
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- MDM2 and MDM4 are proteins that regulate the p53 tumor suppressor, often overexpressed in cancers, leading to clinical trials targeting their interaction with p53.
- A study of bone marrow samples from 111 patients with various types of leukemia found low protein levels of MDM2 and MDM4 in those with high marrow blasts (>5%), while mRNA levels remained similar across samples.
- The low protein expression of MDM2 and MDM4 was linked to worse survival outcomes, highlighting a disconnect between mRNA and protein levels and suggesting a reevaluation of using MDM2 and MDM4 inhibitors in advanced myeloid cancers.
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- * A total of 79 patients participated, and the primary goal was to assess the cumulative molecular response rates over 12 months, with results showing significant rates of deep molecular response at 5 years.
- * While grade 3 neutropenia was common, it didn't lead to severe infections, and most patients continued the Peg-IFN treatment for a substantial time, resulting in notable molecular response rates after 12 and 24 months.
Musculoskeletal (MSK) pains have been reported during TKI treatment or after its discontinuation in patients with chronic myeloid leukemia (CML). We hypothesized that MSK pains originate from calcific tendinopathy according to preliminary clinical observations. We conducted a retrospective study including CML patients divided into three groups: patients with MSK pain during TKI treatment; asymptomatic patients during TKI treatment; patients with MSK pain after TKI discontinuation.
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- Myeloproliferative neoplasms (MPNs) are rare in individuals under 25, and a study examined 444 such patients over a median follow-up of 9.7 years across 38 centers globally.
- The study found that 11.1% had a history of thrombosis, with higher risks associated with the JAK2V617F mutation and hyperviscosity symptoms, while new thrombotic and hemorrhagic events occurred at significant rates.
- It highlighted that disease transformation, particularly to myelofibrosis, was common, with splenomegaly identified as a new risk factor, indicating a need for updated management guidelines for young MPN patients.
Myeloproliferative neoplasms (MPN) are a group of blood cancers in which the bone marrow (BM) produces an overabundance of erythrocyte, white blood cells, or platelets. Philadelphia chromosome-negative MPN has three subtypes, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The over proliferation of blood cells is often associated with somatic mutations, such as , , and .
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- The study investigates the transformation of chronic myeloproliferative neoplasms (MPN) to leukemia, highlighting TP53 mutations as a crucial factor, though their proliferation advantage requires a selection process.
- MDM2 inhibitors, which can protect normal p53 from degradation, show potential in treating TP53-mutated cells, but their effects in this context are not well-studied until now.
- The research reveals that TP53 mutations typically occur late in MPN development, predominantly within the driver clone, and it introduces an in vitro test that can predict the emergence of TP53-mutated cells in response to MDM2 inhibitors.
We have reconciled steady-state and stress hematopoiesis in a single mathematical model based on murine experiments and with a focus on hematopoietic stem and progenitor cells. A phenylhydrazine stress was first applied to mice. A reduced cell number in each progenitor compartment was evidenced during the next 7 days through a drastic level of differentiation without proliferation, followed by a huge proliferative response in all compartments including long-term hematopoietic stem cells, before a return to normal levels.
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- * They found that low erythropoietin levels (≤3.3 mUI/ml) and JAK2 mutations had similar positive predictive values for identifying true polycythemia, around 90% for both tests.
- * Notably, very low erythropoietin levels (≤1.99 mUI/ml) were 100% predictive for diagnosing polycythemia vera, suggesting a need to rethink how erythropoietin is used in diagnostic criteria for this disease.
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- The study looked at how different gene mutations affect the health of people with myelofibrosis, a type of blood disease.
- Researchers analyzed 479 patients and grouped them based on specific mutations to see how these groups relate to worsening conditions or death.
- They found that mutations in certain genes like TP53 and high-risk genes made it more likely for patients to get worse or die, while a mutation in the ASXL1 gene alone didn’t have a significant negative impact.
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- Interferon α (IFNα) is commonly used to treat myeloproliferative neoplasms (MPNs), but it rarely completely eliminates the disease.* -
- This study found that arsenic trioxide (ATO) significantly enhances the growth-suppressing effects of IFNα on JAK2V617F-driven hematopoietic cells by targeting a key gene called PML.* -
- The combination of IFNα and ATO in a mouse model of MPN led to accelerated and improved treatment responses, suggesting that this combo could be highly effective in clinical settings, even when the PML gene is intact.*
The role of ribosome biogenesis in erythroid development is supported by the recognition of erythroid defects in ribosomopathies in both Diamond-Blackfan anemia and 5q- syndrome. Whether ribosome biogenesis exerts a regulatory function on normal erythroid development is still unknown. In the present study, a detailed characterization of ribosome biogenesis dynamics during human and murine erythropoiesis showed that ribosome biogenesis is abruptly interrupted by the decline in ribosomal DNA transcription and the collapse of ribosomal protein neosynthesis.
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- * A study involving 80 MPN-SVT patients over an 11-year median follow-up found that 13% experienced severe hematologic outcomes, linked to higher JAK2 mutation levels and other genetic mutations.
- * High-risk patients, making up 29% of the cohort and showing significant molecular risk factors, had poorer survival rates, suggesting the need for targeted therapy to prevent disease progression.