Studies by several investigators have shown that 12-0-tetradecanoylphorbol-13-acetate (TPA) is an extraordinarily potent stimulator of differentiation of cultured human promyelocytic leukemia cells in vitro. In the present study, TPA was administered to humans by i.v. infusion without irreversible toxicity, and it was shown to have pharmacological activity for the treatment of myelocytic leukem...

IN THE PAST 30 YEARS, the treatment of acute myelocytic leukemia (AML) has considerably evolved and improved. The general evolution in the therapeutic strategy has invariably been on the direction of more aggressive treatment being administered early, as soon as a first complete remission (CR1) has been achieved. The rationale has been to provide maximum antitumor effect with so-called consolid...

The binding of granulocyte colony-stimulating factor (G-CSF) to normal and human acute myeloid leukemia (AML) cells was investigated with radiolabeled recombinant human G-CSF (rhG-CSF). In all 14 cases of primary AML specific receptors for G-CSF were demonstrated on purified blast cells. The average numbers of G-CSF receptors ranged from very low to 428 receptors per cell (mean). Normal granulo...

T HE SENSITIVITY OF LYMPHOCYTES to irradiation provides a rationale for the use of extracorporeal irradiation (ECI ) of the circulating blood to destroy lymphocytes selectively. Since 1962, ECI has been used in various studies, including investigations of lymphocyte physiology and prolongation of allogeneic skin graft survival in calves. These studies1 established the basic feasibility and effe...

Background: Acute myelocytic leukemia (AML) is a clonal malignancy resulting from the accumulation of genetic abnormalities in the cells. Human baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5), encodes survivin, is one of only a handful of genes that is differentially over-expressed in numerous malignant diseases including AML. Methods: The BIRC5 was silenced permanently in two AM...

This article discusses changes in the way hematopoietic stem cell allotransplants may be carried out in the future to treat patients with malignant hematological diseases. Specifically, the focus has shifted away from attempts at eradicating underlying diseases through toxic high-dose chemoradiation therapy towards using the stem cell donor's immune cells for that purpose (allogeneic graft-vers...

Within the past decades, major advances in therapy for chronic myelocytic leukemia, including allogeneic hematopoietic stem cell transplantation, interferon therapy, and, more recently, also therapy with the tyrosine kinase inhibitor imatinib, have entered clinical practice. The impact of these advances on long-term survival on the population level should be disclosed as timely as possible. We ...

We report on a Ph+ chronic myelocytic leukemia (CML) case, cytogenetically characterized by the occurrence of a second Philadelphia (Ph) chromosome in lymphoid blast crisis of T cell lineage. In situ hybridization analyses showed a deletion of translocated c-abl sequences, present on the Ph during chronic state, from both Ph in acute state. Moreover, Southern blot analyses of blastic cells exhi...

Terminal deoxynucleotidyl transferase (TdT), a unique DNA polymerase that does not require a template, is found in thymocytes and marrow Tlymphocytes normally [1,2]. Shortly after these discoveries, McCaffrey et al. [3] described the presence of this enzyme in the leukemic cells of patients with acute lymphoblastic leukemia (ALL) and Sarin et al. [4] discovered that some patients with chronic m...

Heparan sulfate proteoglycans (HSPGs) play important biological roles in cell-matrix adhesion processes and are essential regulators of growth actions. The expression of the different HSPGs in itself is tightly regulated providing strict controls on the activities of the bound ligands. Human liver is a target for a number of pathogens, and HSPGs have been demonstrated in several cases to play a...