0000000000181531
AUTHOR
R H Mertelsmann
Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effects of GM-CSF on polymorphonuclear leukocytes (PMN) more extensively. Using Northern blot analysis, we show that PMN are able to accumulate mRNAs for different cytokines, including tumor necrosis factor-alpha (TNF-alpha); G-CSF, and M-CSF, all of which are involved in inflammation and hematopoiesis. Biological assays and immunoassays demonstrate that PMN translate these mRNAs, except TNF-alpha, into secretory proteins. However, the expression of these cytokines is dependent on stimulation by exogenous…
Identification and purification of human erythroid progenitor cells by monoclonal antibody to the transferrin receptor (T� 67)
Anti-TU 67 is a murine monoclonal antibody that recognizes the transferrin receptor. With respect to hematopoietic cells TU 67 is expressed by human multipotent colony-forming cells (CFU-Mix), erythroid progenitor cells (BFU-E and CFU-E) and a fraction of granulocyte/monocyte colony forming cells, but is not expressed by mature hematopoietic cells including erythrocytes, platelets, lymphocytes, and peripheral blood myeloid cells. The TU 67-positive fraction of normal bone marrow, separated by fluorescence-activated cell sorting (FACS) or immune rosettes, contained 87% of the erythroid progenitor cells. Erythroid progenitor cells were enriched up to 50-fold by using a combination of monoclon…
Low-Dose Aclacinomycin and Intermediate-Dose Cytosine Arabinoside in Relapsed and Refractory Acute Myelogenous Leukemia
Nineteen patients with relapsed or refractory acute myelogenous leukemia were treated with escalating doses of aclacinomycin (ACLA 20–30 mg/m2 daily for 5 days) and intermediate-dose cytosine arabinoside (Ara-C 1 g/m2 twice daily for 4 days). Most patients had received previous therapy with high- or intermediate-dose Ara-C plus mitoxantrone (HAM, IAM) and TAD (6-thioguanine, standard-dose cytosine arabinoside, and daunorubicin). Four patients had had repeated relapses and another three were treated for primary treatment failure following induction with HAM or I AM.
Granulocyte–Macrophage Colony-Stimulating Factor in the Therapy of Adults with De Novo Acute Myeloblastic Leukemia: An Update of a Double-Blind Randomized, Placebo-Controlled Trial
We investigated whether granulocytemacrophage colony-stimulating factor (GMCSF) given concomitantly with chemotherapy (CT) improves the outcome of adults with de novo acute myeloblastic leukemia (AML) by increasing the efficacy of CT and reducing infections. CT included cytarabine (ara-C) daunorubicin, and etoposide (DAV) for induction and early consolidation therapy and one cycle with high-dose (patients aged ≤50 years) or intermediate-dose ara-C (patients aged >50 years) /daunorubicin for late consolidation therapy. Eighty patients were randomized after DAV 1 to receive either GM-CSF (Escherichia coli, 250 µg/m2 per day, s.c.) or placebo starting 48 h prior to DAV II and the subsequent co…
Interleukin 1 stimulates T lymphocytes to produce granulocyte-monocyte colony-stimulating factor.
T lymphocytes are thought to cooperatively interact with monocytes to produce colony-stimulating factors (CSF). However, little is known about monocyte-mediated signals leading to CSF-secretion by T lymphocytes, although soluble monocyte products have been implicated. We have employed monoclonal antibody anti-T3B covalently coupled to CnBr-activated Sepharose 4B beads, to show that multimeric ligation of T cell antigen receptor leads to T cell receptiveness to interleukin 1 (IL-1), as indicated by T cell production of CSF, which induces growth of myeloid progenitor cells into neutrophil, eosinophil, and monocyte colonies. To investigate the molecular basis of these findings, total RNA was e…
Interferon alfa-2c in chronic myelogenous leukemia (CML): hematologic, cytogenetic and molecular-genetic response of patients with chronic phase CML previously resistant to therapy with interferon gamma.
Alpha- and gamma-interferons have been shown to actively suppress hematopoiesis in patients in the chronic phase of chronic myelogenous leukemia in vitro and in vivo. Since both interferons act through different receptors on their hematopoietic target cells, they are expected to be capable of independently inhibiting abnormal blood cell development in patients with chronic myelogenous leukemia. We have utilized recombinant human interferon alfa-2c to treate 11 patients with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase, who were resistant to previous interferon gamma therapy. Ten of the patients were evaluable for hematologic, cytogenetic and molecular-genet…