Publications by authors named "Juliette Soret-Dulphy"
JAK (Janus Kinase) inhibitors, such as ruxolitinib, were introduced a decade ago for treatment of myeloproliferative neoplasms (MPN). To evaluate ruxolitinib's impact on MPN clonal evolution, we interrogate a myelofibrosis patient cohort with longitudinal molecular evaluation and discover that ruxolitinib is associated with clonal outgrowth of RAS pathway mutations. Single-cell DNA sequencing combined with ex vivo treatment of RAS mutated CD34 primary patient cells, demonstrates that ruxolitinib induces RAS clonal selection both in a JAK/STAT wild-type and hyper-activated context.
View Article and Find Full Text PDFGenetic analyses have been included in scoring systems to improve the prognostic stratification of hematologic malignancies. Until now, molecular risk scores have not been included into the practical management of patients with polycythemia vera (PV). In this work, we studied 439 PV patients recruited from 15 French centers and described their mutational landscape using high-throughput sequencing.
View Article and Find Full Text PDFSynergistic effect of concurrent high molecular risk mutations and lower JAK2 mutant variant allele frequencies on prognosis in patients with myelofibrosis-insights from a multicenter study.
Leukemia
January 2025
Article Synopsis
- High-molecular risk (HMR) mutations, such as ASXL1 and IDH, are linked to poorer outcomes in myelofibrosis (MF) patients, particularly when combined with lower levels of the JAK2V617F variant allele frequency (VAF).
- Analysis of 124 MF patients showed that HMR mutations significantly impacted prognosis for those with lower JAK2V617F VAF, while this effect was not observed in patients with higher VAF levels.
- The study's findings indicate that having both HMR mutations and a lower JAK2V617F VAF (≤50%) serves as a strong independent risk factor for survival, improving existing prognostic models and prompting the need for further
Article Synopsis
- A low allele burden (<20%) of the CALR driver mutation is present in 10.8% of patients with CALR-mutated myeloproliferative neoplasms (MPNs), primarily seen in essential thrombocythemia.
- Patients with this low allele burden tend to have a milder disease phenotype.
- Those with less than 20% allele burden also experience a slower progression of their condition compared to patients with a higher allele burden (≥20%).
Article Synopsis
- 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.
Article Synopsis
- 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.
Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES).
View Article and Find Full Text PDFArticle Synopsis
- The Clinical Investigations Center of Saint-Louis Hospital (CIC-1427) specializes in early phase clinical trials and adapted rapidly during the COVID-19 pandemic to ensure patient and staff safety.
- The study aimed to maintain optimal management of patients in trials while adhering to safety protocols set by health authorities.
- New procedures included virtual consultations, remote monitoring, and home delivery of treatments, successfully allowing continued patient follow-up despite the challenges posed by the pandemic.
Article Synopsis
- * 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.
Article Synopsis
- Polycythemia vera is primarily caused by the JAK2V617F mutation, and standard treatments include hydroxyurea and interferon-alpha.
- A study on the drug ropeginterferon alpha-2b demonstrated its effectiveness in inhibiting the growth of JAK2-mutant cells while not affecting normal cells.
- After one year of treatment, patients receiving ropeginterferon showed a 64% reduction in JAK2-mutated erythroid colonies, significantly higher than the 25% reduction seen with hydroxyurea, highlighting its targeted action against malignant progenitors.