Calreticulin Mutations in Myeloproliferative Neoplasms: Comparison of Three Diagnostic Methods.

Calreticulin (CALR) mutations have recently been reported in 70-84% of JAK2V617F-negative myeloproliferative neoplasms (MPN), and this detection has become necessary to improve the diagnosis of MPN. In a large single-centre cohort of 298 patients suffering from Essential Thrombocythemia (ET), the JAK2V617F, CALR and MPL mutations were noted in 179 (60%), 56 (18.5%) and 13 (4.5%) respectively. For the detection of the CALR mutations, three methods were compared in parallel: high-resolution melting-curve analysis (HRM), product-sizing analysis and Sanger sequencing. The sensitivity for the HRM, product-sizing analysis and Sanger sequencing was 96.4%, 98.2% and 89.3% respectively, whereas the specificity was 96.3%, 100% and 100%. In our cohort, the product-sizing analysis was the most sensitive method and was the easiest to interpret, while the HRM was sometimes difficult to interpret. In contrast, when large series of samples were tested, HRM provided results more quickly than did the other methods, which required more time. Finally, the sequencing method, which is the reference method, had the lowest sensitivity but can be used to describe the type of mutation precisely. Altogether, our results suggest that in routine laboratory practice, product-sizing analysis is globally similar to HRM for the detection of CALR mutations, and that both may be used as first-line screening tests. If the results are positive, Sanger sequencing can be used to confirm the mutation and to determine its type. Product-sizing analysis provides sensitive and specific results, moreover, with the quantitative measurement of CALR, which might be useful to monitor specific treatments.

Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis.

BACKGROUND: Refractory anemia with ring sideroblasts associated with marked thrombocytosis was proposed as a provisional entity in the 2001 World Health Organization classification of myeloid neoplasms and also in the 2008 version, but its existence as a single entity is contested. We wish to define the clinical features of this rare myelodysplastic/myeloproliferative neoplasm and to compare its clinical outcome with that of refractory anemia with ring sideroblasts and essential thrombocythemia. DESIGN AND METHODS: We conducted a collaborative retrospective study across Europe. Our database included 200 patients diagnosed with refractory anemia with ring sideroblasts and marked thrombocytosis. For each of these patients, each patient diagnosed with refractory anemia with ring sideroblasts was matched for age and sex. At the same time, a cohort of 454 patients with essential thrombocythemia was used to compare outcomes of the two diseases. RESULTS: In patients with refractory anemia with ring sideroblasts and marked thrombocytosis, depending on the Janus Kinase 2 V617F mutational status (positive or negative) or platelet threshold (over or below 600 × 10(9)/L), no difference in survival was noted. However, these patients had shorter overall survival and leukemia-free survival with a lower risk of thrombotic complications than did patients with essential thrombocythemia (P<0.001) but better survival (P<0.001) and a higher risk of thrombosis (P=0.039) than patients with refractory anemia with ring sideroblasts. CONCLUSIONS: The clinical course of refractory anemia with ring sideroblasts and marked thrombocytosis is better than that of refractory anemia with ring sideroblasts and worse than that of essential thrombocythemia. The higher risk of thrombotic events in this disorder suggests that anti-platelet therapy might be considered in this subset of patients. From a clinical point of view, it appears to be important to consider refractory anemia with ring sideroblasts and marked thrombocytosis as a distinct entity.

Twenty-five years of epidemiological recording on myeloid malignancies: data from the specialized registry of hematologic malignancies of Cote d'Or (Burgundy, France).

BACKGROUND: Epidemiological data on myeloid malignancies are very rare in the literature due to a lack of registration by cancer registries until 2000. The Registry of Hematologic Malignancies of the Côte d'Or Department in France has, however, steadfastly registered data on cases occurring in the Department since 1980, resulting, to date, in a database of over 5,000 cases classified according to the ICD-O-3 classification, following the most recent World Health Organization classification criteria. DESIGN AND METHODS: Twenty-five years of data on myeloid malignancies, including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes and myelodysplastic/myeloproliferative syndromes were analyzed. World population standardized incidence rates were calculated as were as observed and relative survival. RESULTS: Incidence rates per 100,000 inhabitants/year were 2.5 for acute myeloid leukemia, 1.3 for myelodysplastic syndromes, 3.2 for myeloproliferative neoplasms and 0.6 for myelodysplastic/myeloproliferative syndromes. It was found that the incidence rate of myelodysplastic syndromes increased significantly over the period. The median overall survival is 8.9 months for patients with acute myeloid leukemia, 33.8 months for patients with myelodysplastic syndromes, 91.7 months for those with myeloproliferative neoplasms and 26.6 months for patients with myelodysplastic/myeloproliferative syndromes. Observed and relative 20-year survival rates are, respectively, 12% and 13% in acute myeloid leukemia, 2% and 6% in myelodysplastic syndromes and 20% and 34% in myeloproliferative neoplasms. CONCLUSIONS: These population-based data on myeloid malignancies are the first data collected over such a long period and provide interesting information for clinicians and public health authorities, particularly given the paucity of other long-term, population-based data from cancer registries.