Hematopoietic growth factors in acute leukemia.

The hematopoietic growth factors are glycoproteins that can be produced by recombinant DNA technology. They have many potential clinical uses in acute leukemia; several areas have been explored extensively and much data are available from clinical trials. Other areas are of potential interest, but have a paucity of clinical information.

Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B-lineage differentiation capacity.

Relatively little is known about the relationship of lymphoid-associated gene expression to the proliferation and differentiation potential of early human bone marrow lymphoid progenitors. Surface expression of interleukin-7 (IL-7) receptor-alpha (IL-7R alpha), a component of the high-affinity receptor for the lymphoid precursor growth factor IL-7, defined a CD34+ progenitor subset lacking the CD19+ pro-B phenotype but demonstrating markedly enhanced lymphoid clonogenic capacity and the ability to differentiate into pro-B cells in short-term culture. These progenitors expressed mRNA for the lymphoid-associated genes Ig beta, RAG-1, and PAX-5, and were uniformly TdT-positive (TdT+).

Expression and function of adhesion receptors in acute myelogenous leukemia: parallels with normal erythroid and myeloid progenitors.

A variety of adhesion receptors are expressed on the blast cells in patients with acute myelogenous leukemia. The panel of receptors expressed demonstrates heterogeneity just as there is morphologic, histochemical, cytogenetic, and molecular genetic variation between various cases of acute myelogenous leukemia. The adhesion receptors expressed contain representatives of all the main classes of adhesion receptors, but often there is no correlation of the adhesion receptor phenotype with the morphologic or clinical features of acute myelogenous leukemia.

Stem cell factor and stromal cell co-culture prevent apoptosis in a subculture of the megakaryoblastic cell line, UT-7.

The megakaryoblastic cell line, UT-7, is dependent for its growth upon interleukin-3 (IL-3), erythropoietin, or granulocyte-macrophage colony stimulating factor (GM-CSF). A subculture of this line can be maintained in recombinant human c-kit ligand [stem cell factor (SCF)] at 100 ng/ml without requirement for other growth factors. Removal of this subculture from SCF results in rapid loss of viability and decreased proliferation.

Treatment and prognostic factors in acute myeloid leukaemia.

Current induction chemotherapy regimens afford a complete remission in 60 to 80% of patients less than 60 years of age who are diagnosed with acute myelogenous leukaemia. Patients who undergo consolidation with high dose Ara-C or with autologous or allogeneic bone marrow transplantation can expect a long-term disease free survival of 30 to 45%. Which mode of consolidation is preferable is still being investigated in randomized studies.

Patients > or = age 40 years undergoing autologous or allogeneic BMT have regimen-related mortality rates and event-free survivals comparable to patients < age 40 years.

To evaluate the safety and efficacy of marrow transplantation for older adults, the regimen-related mortality and event-free survival for patients > or = 40 years were compared with those for patients < 40 years. Of 148 consecutive patients receiving autotransplants for lymphoma or Hodgkin's disease, 70 were < 40 years and 78 were > or = 40 years at the time of transplant, including 40 who were > or = 50 years and 12 who were > or = 60 years. Eleven patients (16%) in the younger age group died from transplant-related complications compared with 4 (5%) in the older age group.

Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy.

The bone marrow is an important dose-limiting cell renewal tissue for chemotherapy, wide-field irradiation, and autologous bone marrow transplantation. Over the past 5-10 years a great deal has been discovered about the hematopoietic stem cell compartment. Although the toxicity associated with prolonged myelosuppression continues to limit the wider use of chemotherapy and irradiation, ways are being discovered to circumvent this toxicity such as with the increasing use of cytokines.

Effect of stem cell factor on myelopoiesis potential in human Dexter-type culture systems.

Hematopoiesis is influenced by the presence of the hematopoietic microenvironment, and Dexter-type liquid culture systems represent an in vitro representation of some aspects of the microenvironment that are optimal for the propagation of myeloid progenitors. Marrow stromal layers, which constitute part of these culture systems, produce growth factors, including stem cell factor (SCF), a ligand for the c-kit proto-oncogene that has been found to increase detection of myeloid, erythroid, and megakaryocytic progenitors in short-term marrow colony assays. In this work, the role of SCF in Dexter-type culture systems was examined to better define its contribution to steady-state myelopoiesis.

Mechanisms of cytopenia in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) infection often has effects on the hematopoietic system which can be distinguished from the concurrent effects of medications or opportunistic infections. Exactly how the virus mediates these effects remains uncertain, but both in vivo and in vitro studies have pointed up possible direct and indirect modes of hematopoietic suppression. Whether a significant fraction of CD34+ cells in vivo are infected with HIV remains controversial, but most studies using in situ polymerase chain reaction techniques would suggest not.

Characterization of the adherence of normal and leukemic CD34+ cells to endothelial monolayers.

The capacity of normal CD34+ marrow cells and CD34+ leukemic cell lines to adhere to human umbilical vein endothelial cells has been examined. Such interactions have importance since the processes of homing and egress within the marrow microenvironment involve the traverse of sinusoidal endothelium. Umbilical vein endothelial monolayers expressed CD44 and CD54 constitutively, and expression of both E-selectin (ELAM) and vascular cell adhesion molecule-1 (VCAM-1) were inducible with interleukin-1 (IL-1) alpha and beta and tumor necrosis factor (TNF).

Effects of GM-CSF on Ki67 expression and cell cycle traverse in acute myelogenous leukemia specimens and cell lines.

A new strategy in the treatment of acute myelogenous leukemia is to attempt to increase the growth fraction of clonal leukemic cells prior to administration of chemotherapeutic agents by the administration of hematopoietic growth factors. We have studied the effect of GM-CSF on the cell cycle status and Ki67 nuclear antigen expression of AML blasts in vitro. The effect of growth factors and stromal cell co-culture on Ki67 expression in leukemic cell lines was also examined.

CD34+ progenitor cell isolation from blood and marrow: a comparison of techniques for small-scale selection.

The isolation and characterization of primitive hematopoietic cells and their purification in sufficient numbers is important in clinical and research marrow transplantation settings. As systems for large-scale isolation and amplification of such cells are developed, they may assume importance in transplantation, treatment of marrow failure and for gene therapy applications. Such cells have been isolated by numerous techniques and in this work, small-scale isolation of CD34+ cells by two immunoadsorption purification methods is compared with isolation by flow cytometry.

Integrins and adhesive receptors in normal and leukemic CD34+ progenitor cells: potential regulatory checkpoints for cellular traffic.

Multiple adhesion receptors are involved in the interaction of hematopoietic cells with the marrow microenvironment. This work characterizes the expression of various adhesive receptors on normal early hematopoietic precursors and reviews how they might be altered in leukemic states. Early hematopoietic CD34+ cells express CD18, CD11a, CD49d, CD49e, CD44, ICAM-1, and ICAM-3.

Cytokine regulation of early human lymphopoiesis.

An in vitro culture system in which bone marrow-derived fibroblast-like cells support the growth of TdT+ colonies derived from CD34+/CD10- human bone marrow progenitor cells has recently been described. The regulatory role of cytokines during early B lineage commitment was investigated using this culture system. Expression of IL-7, a cytokine that induces proliferation of B cell precursors, was detectable in the adherent layer by PCR and bioassay.

One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome.

Purpose: One hundred autotransplants for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were examined prospectively to identify variables with prognostic significance.

Patients And Methods: Ninety-six patients with relapsed or refractory HD or NHL underwent 100 autotransplants. Patients received high-dose carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem-cell rescue.

Autografting in chronic myelogenous leukemia followed by immunotherapy.

Patients with chronic myelogenous leukemia (CML) can be cured with allogeneic bone marrow transplantation. Over the past decade, it has become clear that immunological mechanisms, in the form of graft-versus-leukemia, constitute an integral part of this therapy. Because of limitations imposed by a lack of suitable donors, age, and toxicity, only a minority of patients can be offered allogeneic bone marrow transplantation (BMT).

Phenotypic characterization of the human fibrous histiocytoma giant cell tumor (GCT) cell line and its cytokine repertoire.

The pleiotropic nature of malignant fibrous histiocytomas (MFH) is manifested as mixed cellular infiltrates consisting of myofibroblasts, histiomonocytes, and neutrophils. We detail in this report the phenotypic characteristics of the human fibrous histiocytoma giant cell tumor (GCT) cell line that establish its mesenchymal origin. The latter is underscored by the ability of GCT cells to express mRNA for transforming growth factor beta (TGF-beta) as well as both A and B chains of platelet-derived growth factor (PDGF).

In vitro erythroid effects of human stem cell factor in a case of human immunodeficiency virus-related chronic parvovirus B19 induced anemia.

Chronic B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1) is one cause of reversible anemia in this patient group. This report describes a case of concurrent HIV-1 and B19 parvovirus infection with pure red cell aplasia in which the anemia resolved with gammaglobulin treatment. When cultured in vitro with recombinant human stem cell factor, the red blood cell precursors from this patient demonstrated increases in both number and size, suggesting that simultaneous infection with B19 parvovirus and HIV-1 does not preclude a response to erythroid-acting growth factors.

Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells.

Adhesion of hematopoietic progenitor cells to marrow-derived adherent cells has been noted for erythroid, myeloid, and lymphoid precursors. In this report, we have characterized very late antigen (VLA) integrin expression on normal CD34+ marrow progenitors, on leukemic cell lines, and on blasts from patients with acute myelogenous or monocytic leukemias. CD34+ progenitor cells expressed the integrin beta 1 chain (CD29), VLA-4 alpha (CD49d), and VLA-5 alpha (CD49e).

Tissue-restricted accumulation of a ribosomal protein mRNA is not coordinated with rRNA transcription and precedes growth of the sea urchin pluteus larva.

We have identified an mRNA that encodes a protein, SpS24, of the small ribosomal subunit in the sea urchin, Strongylocentrotus purpuratus. RNA blot and in situ hybridization analyses show that the SpS24 gene is active during early oogenesis, downregulated in the mature egg and during cleavage, and reactivated in the early blastula. The mRNA then increases in abundance at least 100-fold.

Cytokine effects and role of adhesive proteins and Fc receptors in human macrophage-mediated antibody dependent cellular cytotoxicity.

Mononuclear phagocytes participate in host immunological defense against tumors. We have investigated the role of selected recombinant cytokines on human macrophage-mediated tumor cytotoxicity in vitro utilizing a human colon cancer cell line target, SW1116, and murine monoclonal antibody 17-1A. Blood monocytes were kept in continuous culture to allow differentiation into macrophages.

State of the art; the hypereosinophilic syndromes.

Many disease states such as parasitic infestations, malignancies, collagen vascular diseases, and allergies are associated with eosinophilia. The diagnosis of idiopathic hypereosinophilic syndrome (HES) requires a persistent elevation in the total eosinophil count (greater than 1500/mm3) for over 6 months, associated organ damage and no detectable underlying cause. This review provides an updated summary of the cytokine cascade that controls eosinophil production and delineates our current understanding of the clinical features of hypereosinophilic states.

Treatment patterns in low-grade non-Hodgkin's lymphomas: a single institution study.

Ninety-two cases of low-grade non-Hodgkin's lymphoma were examined retrospectively to assess to what extent treatment deferral is practiced at a single university hospital with a local referral base. Clinical characteristics of this patient group were also analyzed; 70% of these cases were of nodular lymphocytic, poorly differentiated (NLPD) histology, and 74% were stage III or IV. Twenty-two cases were not treated initially.