The thymidine dideoxynucleoside analog, alovudine, inhibits the mitochondrial DNA polymerase γ, impairs oxidative phosphorylation and promotes monocytic differentiation in acute myeloid leukemia.

Mitochondrial DNA encodes 13 proteins that comprise components of the respiratory chain that maintain oxidative phosphorylation. The replication of mitochondrial DNA is performed by the sole mitochondrial DNA polymerase γ. As acute myeloid leukemia (AML) cells and stem cells have an increased reliance on oxidative phosphorylation, we sought to evaluate polymerase γ inhibitors in AML.

Emerging therapies for acute myeloid leukemia: translating biology into the clinic.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor outcome; overall survival is approximately 35% at two years and some subgroups have a less than 5% two-year survival. Recently, significant improvements have been made in our understanding of AML biology and genetics. These fundamental discoveries are now being translated into new therapies for this disease.

Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML.

Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples.

Autoimmunity and novel therapies in immune-mediated thrombocytopenia.

Immune-mediated thrombocytopenic purpura (ITP) is recognized as a cell-specific autoimmune disorder, yet, multifactorial in origin. The development of thrombocytopenia is well proven to be mediated by both humoral (anti-platelet antibodies) and cellular (T-cell) mediated mechanisms. In some cases other autoantibodies are also induced, eg, antinuclear antibody (ANA), anti-dsDNA, and anti-cardiolipin, in addition to anti-platelet antibodies.

[IgM enriched immunoglobulins as a therapy for sepsis and autoimmune diseases].

The importance of natural autoreactive antibodies of the immunogtobulin M (IgM) isotype, raised the issue of the innate immune response being immunoregulatory. These antibodies have low affinity and a wide range of specificity, thus acting as protective autoantibodies. Bearing this in mind, many have proposed the therapeutics potential of IgM enriched intravenous immunoglobulin (IVIg) in sepsis and in autoimmune diseases.

Coronary Artery Disease in an Asymptomatic Population Undergoing a Multidetector Computed Tomography (MDCT) Coronary Angiography.

Aim: To assess the prevalence of coronary artery disease (CAD) in asymptomatic subjects using multidetector computed tomography (MDCT) and its relationships to demographic and clinical risk factors.

Material And Method: We enrolled consecutive asymptomatic volunteers with no evidence of ischemic heart disease that underwent MDCT for the early detection of CAD. All MDCT findings were correlated with demographic and risk factors.