The requirement of c-Myb during erythropoiesis spurred an interest in identifying c-Myb target genes that are important for erythroid development. Here, we determined that the neuropeptide neuromedin U (NmU) is a c-Myb target gene. Silencing NmU, c-myb, or NmU's cognate receptor NMUR1 expression in human CD34(+) cells impaired burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythro...

Juvenile chronic myelocytic leukemia (JCML) is a rare hematopoietic neoplasia of early childhood with distinct hematologic and biochemical features. We studied the biologic properties and the globin synthetic profiles of JCML erythroid cells both in vivo and in vitro from a total of 24 patients. In these cases we observed the exuberant colony-forming unit-macrophage (CFU-M) colony growth, as re...

Hematopoietic reconstitution following syngeneic bone marrow transplantation with graded doses of untreated and drug-treated bone marrow was studied in B6D2F1 mice. Granulocyte-macrophage colony-forming units (CFU-GM) and spleen colony-forming units (CFU-S) showed similar in vitro drug sensitivities. Both the speed of hematologic recovery and survival of mice transplanted with untreated or drug...

Osteoclasts are bone resorbing cells of hematopoietic origin; however, a progenitor cell population that gives rise to mature osteoclasts remains elusive. We have characterized a unique cell surface phenotype of clonogenic osteoclast progenitors (colony-forming unit-osteoclast [CFU-O]) and obtained a marrow cell population selectively enriched for these progenitors. Whole bone marrow cells were...

We studied the cell kill induced by granulocyte-macrophage colony-stimulating factor (GM-CSF ) fused to Diphtheria Toxin (DT-GM-CSF ) in acute myeloid leukemia (AML) samples and in populations of normal primitive hemopoietic progenitor cells. AML samples from three patients were incubated in vitro with 100 ng/mL DT-GM-CSF for 48 hours, and AML cell kill was determined in a proliferation assay, ...

This study reports the development of an assay, the Pre-colony-forming unit (CFU) assay, which detects human hematopoietic precursors. The Pre-CFU assay is based on the observation that precursors to CFU-granulocyte-macrophage (CFU-GM) that are undetectable in clonogenic assays differentiate into CFU-GM preferentially following treatment in suspension culture with recombinant human interleukin-...

Adenoviral gene transfer to primitive hematopoietic progenitor cells (HPCs) would be useful in gene therapy applications where transient, high-level transgene expression is required. In the present investigations, we have used an adenoviral vector expressing the green fluorescent protein (AdGFP) to quantify transduction of primitive HPCs and assess adenoviral-associated toxicity in long-term cu...

The cycling of blood cell counts in grey collie dogs with cyclic hematopoiesis can be eliminated by treatment with oral lithium carbonate. To explore the mechanism by which lithium alters this stem cell disorder, studies of bone marrow granulocyte-macrophage progenitor cells (CFU-C), neutrophil colony-forming cells (neutrophilic CFU-C), and colony-stimulating activity (CSA) were performed. In u...

To investigate the relatedness of soluble and pelletable vesicular erythroid burst-promoting activity (BPA) present in lymphocyte-conditioned medium (LCM), we immunized rabbits with partially purified lymphocyte plasma membranes and tested the antisera for biological and immunologic crossreactivity with LCM and its component fractions. When preincubated with IgG purified from post-immune but no...

Three N-formylated oligopeptides with different known activities as chemotactic factors for leukocytes were studied to determined if these mediators affect the in vitro proliferation of myelomonocytic colony-forming cells (CFU-C) recovered from murine bone marrow. All three oligopeptides inhibited CFU-C growth in a dose-dependent fashion that correlated with their relative potencies as chemotac...