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.

The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia.

Background: Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia.

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.

First and second line imatinib treatment in chronic myelogenous leukemia patients expressing rare e1a2 or e19a2 BCR-ABL transcripts.

During the formation of the Philadelphia (Ph) chromosome, in the majority of chronic myelogenous leukemia (CML) patients, the chromosome 22 breakpoint is located in the major breakpoint cluster region of the BCR gene (M-bcr). Minor and micro breakpoint cluster regions (m-bcr with e1a2 transcript and micro-bcr with e19a2 transcript) are rarely affected and have been suggested to be associated with peculiar CML phenotypes. Despite the different clinical characteristics, it is currently not established, whether different therapeutic options are preferably recommended for the treatment of e1a2 or e19a2 CML.

[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.

Apoptosis induction by retinoids in eosinophilic leukemia cells: implication of retinoic acid receptor-alpha signaling in all-trans-retinoic acid hypersensitivity.

Hypereosinophilic syndrome (HES) has recently been recognized as a clonal leukemic lesion, which is due to a specific oncogenic event that generates hyperactive platelet-derived growth factor receptor-alpha-derived tyrosine kinase fusion proteins. In the present work, the effect of retinoids on the leukemic hypereosinophilia-derived EoL-1 cell line and on primary HES-derived cells has been investigated. We show that all-trans-retinoic acid (ATRA) inhibits eosinophil colony formation of HES-derived bone marrow cells and is a powerful inducer of apoptosis of the EoL-1 cell line.

[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.

Complement Synthesis Influencing Factors Produced by Acute Myeloid Leukemia Blast Cells.

In a previous study, we found hypercomplementaemia in the sera of acute myeloid leukemia patients. In this study we show that the supernatants of mononuclear cells, derived from peripheral blood taken in the blastic phase, from patients with acute myeloid leukemia (CM-AML) increased the in vitro complement protein synthesis of HepG2 hepatocellular carcinoma cells. This effect of CM-AML was mediated by heat labile soluble factors and involved the synthesis of mRNA and protein.