A new dual translocation of chromosome 14 in a pediatric Burkitt lymphoma/leukemia patient: t(8;14) and t(14;15).

Burkitt lymphoma/leukemia (BL/L) is an aggressive mature B-cell malignancy cytogenetically characterized by the translocation t(8;14)(q24;q32) or its variants, which determines the juxtaposition of the MYC oncogene to one of the three immunoglobulin loci. In addition to MYC translocations, different secondary genetic abnormalities have been described, some of them with prognostic significance. However, dual translocations of chromosome 14, except those involving chromosome 18, are very rare events in this pathology. Herein, we present the coexistence of translocations t(8;14) and t(14;15) in a pediatric BL/L patient. To our knowledge, this is the first report of a translocation t(14;15)(q32;q22) as a secondary alteration in a BL/L patient. The patient had multiple complications at diagnosis but he evolved favorably reaching complete remission. The description of new secondary alterations in this pathology as well as their impact on clinical evolution, add information to the biological characterization of BL, contributing to a higher accuracy in the diagnosis and/or prognosis of the disease.

Reaction of human UMP-CMP kinase with natural and analog substrates.

UMP-CMP kinase catalyses an important step in the phosphorylation of UTP, CTP and dCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies. The reactivity of human UMP-CMP kinase towards natural substrates and nucleotide analogs was reexamined. The expression of the recombinant enzyme and conditions for stability of the enzyme were improved. Substrate inhibition was observed for UMP and CMP at concentrations higher than 0.2 mm, but not for dCMP. The antiviral analog l-3TCMP was found to be an efficient substrate phosphorylated into l-3TCDP by human UMP-CMP kinase. However, in the reverse reaction, the enzyme did not catalyse the addition of the third phosphate to l-3TCDP, which was rather an inhibitor. By molecular modelling, l-3TCMP was built in the active site of the enzyme from Dictyostelium. Human UMP-CMP kinase has a relaxed enantiospecificity for the nucleoside monophosphate acceptor site, but it is restricted to d-nucleotides at the donor site.

Sugar derivatives as new 6-phosphogluconate dehydrogenase inhibitors selective for the parasite Trypanosoma brucei.

Sugar derivatives mimicking compounds which take part in the catalysed reaction have been assayed as alternative substrates and/or competitive inhibitors of 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Phosphonate analogues have been synthesised and the new compound 5-deoxy-5-phosphono-D-arabinonate shows good selectivity towards the parasite enzyme. A number of 4-carbon and 5-carbon aldonates are strong inhibitors of the parasite enzyme with K(i) values below the substrate K(m) and some acyl derivatives are also potent inhibitors. At least five of the compounds showing a significant selectivity for the parasite enzyme represent leads for trypanocidal drugs against this recently validated target.

Peptides derived from the heptad repeat region near the C-terminal of Sendai virus F protein bind the hemagglutinin-neuraminidase ectodomain.

Previously, we showed that Sendai virus fusion protein (F) acts as an inhibitor of neuraminidase activity of hemagglutinin-neuraminidase (HN) protein. Here we report that synthetic peptides derived from the heptad repeat region proximal to the transmembrane domain (HR2) of Sendai virus F inhibit fusion and enhance the enzymatic activity of the HN. This occurs on the virus-bound HN and on its soluble globular head. The enhancing effect on virus-bound HN is reversible and depends on the presence of F. The data indicate that, by binding to the HN ectodomain, the HR2 peptides abolish the F inhibition of HN and disrupt the communication between the F and HN essential to promote virus-cell fusion.