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Objectives: To detect relative frequency of anaplastic lymphoma kinase (ALK-1) gene abnormality in diffuse large cell lymphoma (DLCL) using fluorescence in situ hybridization (FISH), and correlate its presence with clinicopathological features which may be useful for choice of therapy and predict survival in newly diagnosed cases. Patients and methods: A prospective study was done between March 2004 and October 2009. Fifty patients newly diagnosed with DLCL were enrolled into the study. Immunophenotyping was done and detection of ALK-1 gene abnormalities were carried out by immunohistochemically (IHC) and FISH. Patients that proved to be ALK-1 positive were treated with standard cyclophosphamide--hydroxy-daunorubicin-oncovin-prednisone (CHOP) protocol. Results: All ALK +ve patients achieved complete remission (CR) vs. 93.5% CR and 6.5% partial remission (PR) for ALK--ve patients respectively. Disease free survival (DFS) at 24 months was 81.8% in the CHOP-14 group (ALK−1-) vs. 100% for the CHOP-21 group (ALK-1+). Overall survival (OS) at 30 months was 80.4% in the CHOP-14 group vs. 100% for the CHOP-21 group. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant bleeding disorder and has two variants, HHT1 and HHT2, associated with mutations in the ENG and ALK-1 genes, respectively. We identified one Chinese HHT2 family to investigate the pathogenic gene and its possible mechanism of action by mutation screening and functional study. One substitution mutation (1717C>T) in exon 10 of the ALK-1 was found by sequencing of all exons of ENG and ALK-1 and caused a R479X mutation in the ALK-1 protein. ALK-1 mRNA and plasma thrombomodulin were measured by real-time quantitative PCR and ELISA, respectively. There was no significant difference in the expression levels of ALK-1 mRNA between patients and healthy individuals. A significantly higher level of thrombomodulin was found in HHT patients. These findings indicate that the mutation causes truncation of the ALK-1 protein at the post-transcriptional level; the plasma thrombomodulin may provide an easy diagnostic indicator in HHT patients. [ABSTRACT FROM AUTHOR]