Identification of Two Novel Gene Variants in Primary Familial Polycythemia: Case Report and Literature Review.

Primary familial and congenital polycythemia is a rare disease characterized by an increase in red cell mass that may be due to pathogenic variants in the EPO receptor () gene. To date, 33 genetic variants have been reported to be associated. We analyzed the presence of variants in two patients with polycythemia in whom pathogenic variants had been previously discarded.

Molecular and cytogenetic characterization of myelodysplastic syndromes in cell-free DNA.

Molecular and cytogenetic studies are essential for diagnosis and prognosis in patients with myelodysplastic syndromes (MDSs). Cell-free DNA (cfDNA) analysis has been reported to be a reliable noninvasive approach for detecting molecular abnormalities in MDS; however, there is limited information about cytogenetic alterations and monitoring in cfDNA. We assessed the molecular and cytogenetic profile of a cohort of 70 patients with MDS by next-generation sequencing (NGS) of cfDNA and compared the results to sequencing of paired bone marrow (BM) DNA.

Polycythemia Vera and Essential Thrombocythemia Patients Exhibit Unique Serum Metabolic Profiles Compared to Healthy Individuals and Secondary Thrombocytosis Patients.

Most common myeloproliferative neoplasms (MPNs) include polycythemia vera (PV) and essential thrombocythemia (ET). Accurate diagnosis of these disorders remains a clinical challenge due to the lack of specific clinical or molecular features in some patients enabling their discrimination. Metabolomics has been shown to be a powerful tool for the discrimination between different hematological diseases through the analysis of patients' serum metabolic profiles.

Circulating cell-free DNA improves the molecular characterisation of Ph-negative myeloproliferative neoplasms.

Genetic studies in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) are essential to establish the correct diagnosis and to optimise their management. Recently, it has been demonstrated that it is possible to detect molecular alterations analysing cell-free DNA (cfDNA) in plasma samples, which is known as liquid biopsy. We have assessed the molecular profile of a cohort of 107 MPN patients [33 polycythaemia vera (PV), 56 essential thrombocythaemia (ET), 14 primary myelofibrosis (PMF) and 4 unclassifiable MPN] by next-generation sequencing (NGS) using cfDNA and paired granulocyte DNA.

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk.

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis.

Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study.

Background: Polycythaemia vera is a myeloproliferative neoplasm characterised by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow due to mutations in the Janus kinase 2 (JAK2) gene. Ruxolitinib, a JAK 1 and JAK 2 inhibitor, showed superiority over best available therapy in a phase 2 study in patients with polycythaemia vera who were resistant to or intolerant of hydroxyurea. We aimed to compare the long-term safety and efficacy of ruxolitinib with best available therapy in patients with polycythaemia vera who were resistant to or intolerant of hydroxyurea.

Pemphigus-like hypereosinophilic syndrome with FIP1L1-PDGFRA fusion gene: A challenging and uncommon clinical presentation.

Hypereosinophilic syndrome (HES) is often associated with cutaneous manifestations, mostly pruritic lesions, urticaria and angioedema. Mucosal lesions are rarely seen in HES but, when present, are usually the first manifestation of the disease. The clinical presentation may be heterogeneous, including erosions, aphthae or ulcers, and can be easily confused with other mucocutaneous disorders.

Rapidly Growing and Aggressive Cutaneous Squamous Cell Carcinomas in a Patient Treated with Ruxolitinib.

Ruxolitinib is a Janus kinase (JAK)1 and JAK2 inhibitor approved for the treatment of myelofibrosis and for polycythemia patients who are resistant or intolerant to hydroxyurea. We report a 72 year-old man patient with polycythemia vera who developed multiple cutaneous squamous cell carcinomas (cSCCs) with keratoacanthoma-like histological features while on treatment with ruxolitinib. Similar lesions have been reported in an isolated patient who also received ruxolitinib.

Thromboembolic events in polycythemia vera.

Thromboembolic events and cardiovascular disease are the most prevalent complications in patients with polycythemia vera (PV) compared with other myeloproliferative disorders and are the major cause of morbidity and mortality in this population. Moreover, a vascular complication such as arterial or venous thrombosis often leads to the diagnosis of PV. The highest rates of thrombosis typically occur shortly before or at diagnosis and decrease over time, probably due to the effects of treatment.

Study of the frequency and reasons for discontinuation of different lines of treatment in patients with multiple myeloma.

The availability of new agents for the treatment of multiple myeloma has allowed the use of multiple lines of treatment, but a percentage of patients do not reach to receive this combination because of toxicity and early death. In this regard, a cross-sectional European study evaluated the management of different lines and discontinuation of treatment in 7635 patients from seven countries in routine clinical practice, finding that 39% of European patients do not receive a second line and that only 4% of patients reach third line in Spain, a figure that is striking when comparing with the rest of the countries. We analyze the frequency and causes of treatment discontinuation in a series of 108 patients from a Spanish University hospital showing that the main reason for permanent treatment discontinuation after finishing first line was to have a response, while death due to disease progression accounted for the main reason in subsequent lines of therapy, with its frequency increasing according to the number of lines received.

Epigenomic profiling of myelofibrosis reveals widespread DNA methylation changes in enhancer elements and as a potential tumor suppressor gene that is epigenetically regulated.

In this study we interrogated the DNA methylome of myelofibrosis patients using high-density DNA methylation arrays. We detected 35,215 differentially methylated CpG, corresponding to 10,253 genes, between myelofibrosis patients and healthy controls. These changes were present both in primary and secondary myelofibrosis, which showed no differences between them.

Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study.

EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both.

Non-driver mutations in patients with JAK2V617F-mutated polycythemia vera or essential thrombocythemia with long-term molecular follow-up.

JAK2V617F monitoring and NGS of non-driver genes was performed in 100 patients with polycythemia vera (PV) or essential thrombocythemia (ET) with long molecular follow-up. Patients who did not progress to myelofibrosis (MF) or acute myeloid leukemia (AML) after more than 10 years (n = 50) showed a low frequency of mutations at first sample (18%) and an incidence rate of 1.7 new mutations × 100 person-years.

Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the Evaluation of Anagrelide Efficacy and Long-term Safety study.

Evaluation of Anagrelide (Xagrid) Efficacy and Long-term Safety, a phase IV, prospective, non-interventional study performed in 13 European countries enrolled high-risk essential thrombocythemia patients treated with cytoreductive therapy. The primary objectives were safety and pregnancy outcomes. Of 3721 registered patients, 3649 received cytoreductive therapy.

Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia.

The influence of driver mutations on leukaemic transformation was analysed in 1747 patients with polycythaemia vera or essential thrombocythaemia. With a median follow-up of 7·2 years, 349 patients died and 62 progressed to acute leukaemia or myelodysplastic syndrome. Taking death as a competing risk, CALR genotype was associated with a lower risk of transformation [subdistribution hazard ratio (SHR): 0·13, 95% confidence interval (CI): 0·2-0·9, P = 0·039], whereas JAK2 V617F showed borderline significance for higher risk (SHR: 2·05, 95% CI: 0·9-4·6, P = 0·09).

MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis.

Background: Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated.

Materials And Methods: We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes.

Risk of thrombosis according to need of phlebotomies in patients with polycythemia vera treated with hydroxyurea.

Hematocrit control below 45% is associated with a lower rate of thrombosis in polycythemia vera. In patients receiving hydroxyurea, this target can be achieved with hydroxyurea alone or with the combination of hydroxyurea plus phlebotomies. However, the clinical implications of phlebotomy requirement under hydroxyurea therapy are unknown.

How to Treat Essential Thrombocythemia and Polycythemia Vera.

Polycythemia vera and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms associated with thrombotic or hemorrhagic complications, and increased risk of transformation to myelofibrosis and acute myeloid leukemia. The main goal of therapy is aimed at preventing vascular events that are the leading cause of morbidity and mortality in these patients. Accordingly, risk stratification is the basis for deciding when to treat a patient with cytoreductive therapy.

Characterization of CD34+ hematopoietic progenitor cells in JAK2V617F and CALR-mutated myeloproliferative neoplasms.

Mutations in JAK2 or CALR are observed in patients with myeloproliferative neoplasms (MPN). To get further insight in the dynamics of the mutant clone, we assessed the mutant allele burden in hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs) and granulocytes from 138 patients [51 polycythemia vera (PV), 58 essential thrombocythemia (ET) and 29 myelofibrosis (MF)]. CALR-mutated ET patients harbored a higher mutant load at progenitor level than JAK2V617F-positive ET (HSCs: 39.

Hematological disorders: a commonly unrecognized cause of acute stroke.

Introduction: Hematological disorders account for about 1.3% of all causes of acute stroke. This systematized review presents updated information on the implications of this category of heterogeneous diseases as a cause of stroke.