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Background: Acquired calreticulin (CALR) gene mutations are one of the molecular hallmarks of essential thrombocythemia (ET). It has been suggested that patients with ET with CALR mutations are associated with a distinct clinical phenotype., Patients and Methods: We evaluated the clinical and molecular features of 150 patients with ET followed over a period of 15 years. The screening for the presence of insertion/deletion mutations in CALR exon 9 was done with a fluorescent polymerase chain reaction/capillary electrophoresis procedure. Sanger sequencing of CALR exon 9 was used for the characterization of mutations and for the analysis of triple-negative patients., Results: CALR mutations were detected in 42 (28%) patients. The most common CALR mutations were type 1 and type 2, which were present in 11 (26.2%) and 20 (47.6%) patients, respectively. Additionally, 10 different small insertion/deletions (3 known and 7 new) were detected in 11 patients, resulting in an altered calreticulin C-terminal end. The clinical characteristics of all CALR+ patients with ET were in line with previously published data for this subset of patients., Conclusion: Our results showed that a wide range of different CALR mutations are associated with a distinct ET clinical phenotype that is associated with the male gender, younger age at diagnosis, higher platelet and lower leukocyte and erythrocyte counts and lower hemoglobin level, and a milder clinical course. The relatively high frequency of new insertion/deletion mutations indicate that the use of fluorescent polymerase chain reaction followed by capillary electrophoresis is the method of choice for the analysis of these defects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Recently, V617F mutation in JAK2 tyrosine kinase gene was established as a marker of myeloproliferation, useful for proving clonality and securing diagnosis in a considerable proportion of the myeloproliferative neoplasms (MPN) The discovery presents a major breakthrough in the understanding of the pathogenesis of the MPN. Moreover, some studies suggest a possible role of the JAK2V617F mutation in the pathogenesis of some specific acute myeloid leukemia (AML) subtypes. To further improve the understanding of the role of JAK2V617F mutations in the pathogenesis and the clinical course of the myeloid malignancies we screened 192 patients with various MPN and AML for the mutations and analyzed the possible association between JAK2V617F mutations and the clinical features of MPNs patients. The frequency of V617F JAK2 mutation was analyzed by theallele-specific PCR assay. Out of 153 cases with known or suspected diagnoses of MPNs, 100 (65.3%) were positive for the JAK2V617F mutation and 53 (34.7%) were negative. In 39 AML cases the mutant allele V617F was not expressed. Correlations of the clinical features at diagnosis and long-term prognosis between the two JAK2-V617F different MPNs groups revealed comparability regarding all tested parameters except for the incidence of thrombotic history. Patients with the mutation had significantly higher incidence of thrombotic complication (38.5%), compared to the group without the mutation (19.2%) (P < 0.005). Our results confirmed the diagnostic significance of JAK2V617F mutation in MPNs and supported the notion that patients with the mutation should be classified in a new entity of MPNs.

B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. Classical staging systems and laboratory features help predict survival in CLL, but they do not distinguish patients who will progress from those whose disease will remain indolent. In recent years, new molecular prognostic factors have emerged that have significantly improved prediction of the risk for disease progression. The mutational status of the immunoglobulin variable heavy chain genes (VH) is one of the major molecular prognostic factors. In this study we evaluated the association between the immunoglobulin VH gene mutation status and the clinical characteristics and outcome in 65 CLL patients that had been followed for a considerably long period at our institution. At diagnosis, patients with unmutated VH genes had higher median lymphocyte counts (P=0.001), higher total tumor mass score (P=0.001) and more often presented at an advance clinical stage (P=0.005) compared to patients utilizing mutated VH genes. Moreover, the median survival of patients with unmutated VH genes was considerably shorter (VH unmutated, 56 months, VH mutated, 125 months; P<0.001). These data confirmed the prognostic value of immunoglobulin VH genes mutational status in CLL, which divides the disease in two prognostic subsets in terms of overall survival and clinical characteristics of the disease. Analysis of the mutational status of the immunoglobulin VH genes may allow for an individualized approach to CLL treatment in the near future.