Publications by authors named "Valerie Ugo"
Genetic 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 PDFPatients with essential thrombocythemia (ET) have a chronic evolution with a risk of hematologic transformation associated with a dismal outcome. Because patients with resistance or intolerance have adverse prognosis, it is important to identify which patient will respond to first-line treatment. We, therefore, aim to describe the association between additional mutations and response to first-line treatment in patients with ET.
View Article and Find Full Text PDFThe aim of our study was to analyze the potential survival benefit associated with hematopoietic stem cell transplantation (HSCT) according to clinicobiological scores, which incorporate mutation-enhanced international prognostic score system (MIPSS) to facilitate decision-making in this context. One transplant (n = 241) and 1 nontransplant cohort (n = 239) were used to test the hypothesis that patients with primary myelofibrosis with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference.
View Article and Find Full Text PDFArticle 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
- 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.
Article Synopsis
- * Researchers analyzed 91 patients and found multiple gene mutations, with FLT3 and NPM1 being the most common; specific mutations were linked to remission success, treatment resistance, and post-relapse mortality.
- * Short-term outcomes were best predicted by general health and performance status, while long-term outcomes were better assessed using genomic classifications, highlighting the need for tailored prognostic systems for older patients, as existing models primarily focus on younger individuals.
Article Synopsis
- Myelofibrosis is a type of blood cancer that leads to symptoms like fatigue and an enlarged spleen, and is often treated with Janus kinase (JAK) inhibitors.
- A recent analysis of seven studies with nearly 2,000 patients compared the effectiveness of four JAK inhibitors—ruxolitinib, fedratinib, pacritinib, and momelotinib—against each other and against a placebo.
- Findings showed that momelotinib and fedratinib were similarly effective as ruxolitinib but had lower toxicity, while pacritinib was less effective first-line but worked well in second-line treatment; choices can depend on individual patient needs, especially regarding side
Article Synopsis
- Immunoglobulin replacement therapy is often recommended for severe hypogammaglobulinemia in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its link to increased infection risk remains unconfirmed.
- A study involving 76 allo-HSCT patients found no significant difference in gamma globulin levels between those who had infections and those who did not during the first 100 days post-transplant.
- The findings suggest that humoral deficiency has a limited role in immune deficiency during this period, raising questions about the necessity of immunoglobulin replacement therapy.
Article Synopsis
- 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.
Article Synopsis
- - Among myeloproliferative neoplasms, polycythemia vera (PV) and essential thrombocythemia (ET) are chronic conditions that can evolve into leukemia, although this progression is rare and has a poor prognosis.
- - A study involving 49 cases of leukemic transformations in PV and ET identified three distinct molecular groups that correlate with different timelines for transformation based on specific genetic mutations.
- - The research revealed that some mutations were present during the chronic phase of the disease, but not all mutations were detectable before the onset of leukemia, indicating that the transformation process may involve varying molecular mechanisms over time.
Article Synopsis
- - The study examines how mutations in calreticulin (CALRm) impact patients with essential thrombocythemia and myelofibrosis, showing that these mutations primarily affect blood cells and lead to early clonal dominance in hematopoietic stem and progenitor cells (HSPC).
- - Type 1 CALRm spreads more easily in lymphoid cells than type 2 CALRm and is linked to a greater increase in various blood progenitors, while both types increase megakaryocytic progenitors and show different effects on signaling pathways.
- - Results indicate that CALRm mutations serve as both initial and phenotypic events in the disease progression, with type 1 CALRm exhibiting a stronger influence on blood
Article Synopsis
- Next-generation sequencing (NGS) is being evaluated for its role in detecting somatic mutations in patients with chronic myeloid malignancies, but its effectiveness in routine clinical decision-making is still uncertain.
- In a multicenter study involving 177 patients, two groups were examined: one focused on identifying clonal hematopoiesis and the other on assessing therapeutic effects of somatic mutations using a specific gene panel.
- The results indicated that NGS significantly aided in making accurate diagnoses for 83% of patients and led to treatment modifications in 19%, highlighting its potential benefits for patient management and healthcare costs.
Article Synopsis
- * Results show that patients with incomplete chimerism have a higher risk of relapse and lower overall survival rates, with a significant correlation between increased recipient DNA and relapse risk.
- * Both chimerism monitoring and WT1 quantification demonstrated comparable effectiveness in predicting relapse, indicating that CD3-negative chimerism monitoring could be a valuable tool for patients lacking specific molecular markers.
Sequential mutational evaluation of CALR -mutated myeloproliferative neoplasms with thrombocytosis reveals an association between CALR allele burden evolution and disease progression.
Laurane Cottin
,
Jérémie Riou
,
Corentin Orvain
,
Jean Christophe Ianotto
,
Françoise Boyer
,
Valérie Ugo
Br J Haematol
March 2020
Article Synopsis
- In myeloproliferative neoplasms (MPN), the measurement of the JAK2V617F allele burden is important for patient prognosis, but the role of CALR mutations is less defined.
- A study involving 45 CALR-mutated essential thrombocythaemia patients combined next-generation sequencing with CALR allele burden evaluation and found TET2 as the most common mutation.
- The research revealed that an increase in CALR allele burden during follow-up is linked to disease progression, suggesting that monitoring this allele may have clinical significance.
Targeted molecular characterization shows differences between primary and secondary myelofibrosis.
Frédéric Courtier
,
Séverine Garnier
,
Nadine Carbuccia
,
Arnaud Guille
,
José Adélaide
,
Valérie Ugo
Genes Chromosomes Cancer
January 2020
Article Synopsis
- Myelofibrosis (MF) can be primary (PMF) or secondary (SMF) and is associated with a higher risk of acute myeloid leukemia (AML) and shorter life expectancy.
- A study using next generation sequencing found that PMF has more ASXL1 and SRSF2 mutations compared to SMF, with specific mutations indicating poorer survival rates in both forms.
- PMF and SMF show distinct molecular profiles influencing their prognosis, suggesting that integrating genetic mutations with existing scoring systems could enhance patient outcome assessments.
WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis.
Blood Cells Mol Dis
March 2019
Article Synopsis
- Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), linked to specific driver mutations in the JAK2, CALR, or MPL genes.
- * The study found that the WT1 transcript is overexpressed in patients with PMF and PV compared to healthy controls, with significantly higher levels in PMF.
- * High levels of the WT1 transcript in PMF are associated with older age, splenomegaly, and thrombocytopenia, and can be a reliable diagnostic marker for PMF when levels exceed 10 copies/10ABL1.
Article Synopsis
- Donor cell leukemia (DCL) is a rare complication that can occur after receiving a stem cell transplant, making it hard to estimate its true incidence; improved testing methods have helped identify it better.
- The article reports on two unique cases of donor cell-derived acute promyelocytic leukemia (APL) in patients who had previously undergone hematopoietic stem cell transplantation (HSCT), highlighting that this issue is quite rare.
- The study emphasizes the need for long-term monitoring of transplant recipients to better understand DCL's genetic factors and responses to treatments like donor lymphocyte infusion, especially as the number of transplants increases globally.