Co-occurrence of Myeloproliferative Neoplasms and Solid Tumors Is Attributed to a Synergism Between Cytoreductive Therapy and the Common TERT Polymorphism rs2736100.

Background: The germline telomerase reverse transcriptase (TERT) rs2736100_C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN).

Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100_C and Janus kinase 2 (JAK2) rs12343867_C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals.

Results: TERT rs2736100_C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.

[Complex molecular genetic algorithm in the diagnosis of myeloproliferative neoplasms].

Introduction: Mutations in Janus kinase 2, calreticulin and thrombopoietin receptor genes have been identified in the genetic background of Philadelphia chromosome negative, "classic" myeloproliferative neoplasms.

Aim: The aim of the authors was to identify driver mutations in a large myeloproliferative cohort of 949 patients.

Method: A complex array of molecular techniques (qualitative and quantitative allele-specific polymerase chain reactions, fragment analyzes, high resolution melting and Sanger sequencing) was applied.

Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations.

Somatic insertions/deletions in the calreticulin gene have recently been discovered to be causative alterations in myeloproliferative neoplasms. A combination of qualitative and quantitative allele-specific polymerase chain reaction, fragment-sizing, high resolution melting and Sanger-sequencing was applied for the detection of three driver mutations (in Janus kinase 2, calreticulin and myeloproliferative leukemia virus oncogene genes) in 289 cases of essential thrombocythemia and 99 cases of primary myelofibrosis. In essential thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%) myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple-negative (11%) cases were identified, while in primary myelofibrosis 56 (57%) Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were identified.

Additional chromosome abnormalities, BCR-ABL tyrosine kinase domain mutations and clinical outcome in Hungarian tyrosine kinase inhibitor-resistant chronic myelogenous leukemia patients.

Background: Additional chromosome abnormalities (ACAs), mutations of the BCR-ABL tyrosine kinase domain (TKD) and BCR-ABL splice variants may cause resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myelogenous leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoid leukemia (ALL).

Methods: Karyotyping and BCR-ABL TKD mutation screening were performed in 71 imatinib-resistant CML patients and 6 Ph+ ALL patients. A total of 56 out of these 77 patients received second-generation TKI.

Simultaneous proteosome inhibition and heat shock protein induction by bortezomib is beneficial in experimental pancreatitis.

The proteosome inhibitor bortezomib is used in the treatment of patients with multiple myeloma. Proteosomes are responsible for the degradation of I-kappaB, the inhibitory protein of transcription factor nuclear factor kappa B (Nf-kappaB). The heat shock protein (HSP) inducing effect of bortezomib is also documented.

HFE C282Y mutation as a genetic modifier influencing disease susceptibility for chronic myeloproliferative disease.

Iron metabolism has been implicated in carcinogenesis and several studies assessed the potential role of genetic variants of proteins involved in iron metabolism (HFE C282Y, TFR S142G) in different malignancies. Few reports addressed this issue with relation to chronic myeloproliferative disorders (CMPD). The aims of our study were (a) to examine the potential associations of CMPD development with genetic modifiers of iron metabolism in a large cohort of CMPD patients; (b) to examine associations of genetic variants of proteins involved in iron metabolism; and acquired JAK2 V617F mutation with clinical characteristics of CMPD.

[Role of the activating mutation Val617Phe of Janus kinase 2 gene in myeloproliferative diseases and significance of its detection].

The Val617Phe point mutation of Janus kinase 2 gene is believed to participate in the pathogenesis of myeloproliferative syndrome characterised by the clonal alteration of hematopoietic stem cells. According to current results, the frequency of Val617Phe activating mutation is around 80% in polycythaemia vera, 35% in essential thrombocythemia, and 50% in chronic idiopathic myelofibrosis. The diagnoses of polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis were so far based on the exclusion of secondary factors as well as bone marrow biopsy histology.

Hepatosplenic gammadelta T-cell lymphoma with ring chromosome 7, an isochromosome 7q equivalent clonal chromosomal aberration.

Hepatosplenic T-cell lymphoma is a rare, clinically aggressive lymphoma. Most cases represent a neoplasm of mature non-activated gammadelta T cells. Isochromosome 7q i(7)(q10) is thought to be the primary cytogenetic abnormality of this disease.

[Prognostic significance of age and karyotype in the treatment of acute myeloid leukemia: results at our center].

Introduction: Treatment outcome in patients with acute myeloid leukemia are determined by prognostic factors.

Aim And Methods: Between January 1996 and December 2001 160 patients were treated with newly diagnosed acute myeloid leukemia. Treatment results were analysed according to the age and cytogenetics.

Salvage chemotherapy with donor lymphocyte infusion and STI 571 in a patient relapsing with B-lymphoblastic phase chronic myeloid leukemia after allogeneic bone marrow transplantation.

Relapse is the main cause of treatment failure following hematopoietic stem cell transplantation for blastic phase chronic myeloid leukemia. Treatment options including donor lymphocyte infusion, second transplantation, interferon- and re-induction chemotherapy are often unsuccessful. We report a patient with blastic phase chronic myeloid leukemia relapsing after allogeneic stem cell transplantation.

IL-6 and lipoprotein(a) [LP(a)] concentrations are related only in patients with high APO(a) isoforms in monoclonal gammopathy.

We have investigated the influence of apo(a) genetics on the relationship between interleukin (IL)-6, and lipoprotein (a) [Lp(a)] levels in 154 patients with monoclonal gammopathy and 189 healthy subjects. No significant differences in Lp(a) levels and distribution of subjects with different sizes of apo(a) isoforms were found between patients and healthy controls. Relationship between IL-6 and Lp(a) levels was strongly dependent on the size of apo(a) isoforms.