Vascular endothelial growth factor signaling in acute myeloid leukemia

This review is designed to provide an overview of the current literature concerning vascular endothelial growth factor signaling (VEGF) in acute myeloid leukemia (AML). Aberrant VEGF signaling operates in the bone marrow of AML patients and is related to a poor prognosis. The altered signaling pathway demonstrated to interfere in several autocrine and paracrine signaling pathways. VEGF signaling promotes autocrine AML blast cell proliferation, survival, and chemotherapy resistance. In addition, VEGF signaling can mediate paracrine vascular endothelial cell-controlled angiogenesis in AML. Both effects presumably explain the association of high VEGF levels and poor therapeutic outcome. More recently, researches focusing on bone marrow stem cell niches demonstrate a role for VEGF signaling in the preservation of several cell types within these niches. The bone marrow niches are proposed to be a protective microenvironment for AML cells that could be responsible for relapses in AML patients. This implies the need of sophisticated VEGF-targeted therapeutics in AML therapy strategies. This review highlights our current understanding of aberrant VEGF signaling in AML, appoints the interference of VEGF signaling in the AML-associated microenvironment, and reflects the novelty of current VEGF-targeted therapeutics used in clinical trails for the treatment of AML.     

DNA methylation in chicken brain and liver

Adult chicken brain DNA is subject to a developmental alteration of methylation at HpaII sites flanking 4, 1, 0.8 and 0.7 kilobase sequences. This change is not evident in adult chicken liver DNA and 1-day-old chick brain and liver DNAs, suggesting tissue specificity and age-dependency in DNA methylation.     

DNA methylation in chicken brain and liver

Summary Adult chicken brain DNA is subject to a developmental alteration of methylation atHpaII sites flanking 4, 1, 0.8 and 0.7 kilobase sequences. This change is not evident in adult chicken liver DNA and 1-day-old chick brain and liver DNAs, suggesting tissue specificity and age-dependency in DNA methylation.     

DNA methylation in dedifferentiating plant pith tissue

Summary A dedifferentiating system in plant tissue (Nicotiana glauca pith tissue grown in vitro) is described, where DNA amplification was demonstrated both cytologically and biochemically. In this system a DNA statellite is synthesized and reaches its maximum around 48 h of culture. This satellite is highly methylated and there are 2 methylation and there are 2 methylation peaks around 24 and 72 h of culture. The results are discussed in relation to recent evidence of the involvement of methylation in differentiation processes.     

DNA methylation of fly genes and transposons

The use of anti-5-methylcytosine antibodies in affinity columns allowed the identification of methylated sequences in the genome of Drosophila melanogaster adults. In view of the presence of transposable elements amongst the identified sequences, it has been suggested that DNA methylation is involved in transposon control in the fly genome. On the contrary, a reanalysis of these data furnishes several intriguing elements that could raise new questions about the role that DNA methylation plays in the fly genome. The aim of the present paper is to discuss some features that emerge from the analysis of the identified methylated sequences. Received 26 January 2006; received after revision 8 May 2006; accepted 2 June 2006     

Ropalocytosis in acute leukemia

Summary Unusual club-shaped processes have been seen in the lymphoblasts in the peripheral blood of case of untreated acute leukemia. These arose from a single area of the cell surface and appeared identical to the morphologic change seen in ropalocytosis in red cells. Red cells in the peripheral blood were also affected.     

Emerging connections between DNA methylation and histone acetylation

Modifications of both DNA and chromatin can affect gene expression and lead to gene silencing. Evidence of links between DNA methylation and histone hypoacetylation is accumulating. Several proteins that specifically bind to methylated DNA are associated with complexes that include histone deacetylases (HDACs). In addition, DNA methyltransferases of mammals appear to interact with HDACs. Experiments with animal cells have shown that HDACs are responsible for part of the repressive effect of DNA methylation. Evidence was found in Neurospora that protein acetylation can in some cases affect DNA methylation. The available data suggest that the roles of DNA methylation and histone hypoacetylation, and their relationship with each other, can vary, even within an organism. Some open questions in this emerging field that should be answered in the near future are discussed.     

Virus-like particles in acute lymphoblastic leukemia

Zusammenfassung In Knochenmark-Monocyten eines fünfjährigen Mädchens konnten im Cytoplasma Einschlüsse beobachtet werden, die mit gewundenen Membranen und virusähnlichen Partikeln fegüllt waren.     

Anomalous incidence of chromosome 1 gh+ in chronic myeloid leukemia]

Chromosome C variants have been analyzed in individuals with hematological disorders. The incidence of chromosome 1 gh+ was significantly enhanced in CML patients (20/24) compared with controls (8/17). The distribution of C-variants of chromosomes 9 and 16 was not different in these individuals.     

Clonogenic growth of acute non-lymphocytic leukemia cells in serum-free medium

We devised a serum-free medium for growth of leukemic colony-forming units (CFU-L), enriched with albumin, transferrin, lipids, insulin, hydrocortisone and oligoelements. Blast cells from 15 patients affected by acute non-lymphocytic leukemia were grown in this medium in the presence of human placental conditioned medium obtained under serum-free conditions (sfHPCM). Their clonogenic growth was comparable with that obtained in a serum-containing system. Furthermore, when serum-free cultures were carried out in absence of sfHPCM, either CFU-L growth was prevented or, if clones were obtained, the cultures showed a marked decrease in clonogenicity, indicating their strict dependence on growth factors.     

Clonogenic growth of acute non-lymphocytic leukemia cells in serum-free medium

Summary We devised a serum-free medium for growth of leukemic colony-forming units (CFU-L), enriched with albumin, transferrin, lipids, insulin, hydrocortisone and oligoelements. Blast cells from 15 patients affected by acute non-lymphocytic leukemia were grown in this medium in the presence of human placental conditioned medium obtained under serum-free conditions (sfHPCM). Their clonogenic growth was comparable with that obtained in a serum-containing system. Furthermore, when serum-free cultures were carried out in absence of sfHPCM, either CFU-L growth was prevented or, if clones were obtained, the cultures showed a marked decrease in clonogenicity, indicating their strict dependence on growth factors.