The identification and characterization of a novel human differentiation-inhibiting protein that selectively blocks erythroid differentiation.

We have isolated a novel inhibitor of erythropoietic differentiation from the plasma of a patient suffering from idiopathic pure red cell aplasia. This differentiation-inhibiting protein (DIP) specifically blocked the differentiation of human burst-forming unit-erythroid (BFU-E), but not colony-forming unit-erythroid (CFU-E) cells. DIP also blocked the maturation of murine BFU-E cells, but not CFU-E or CFU-granulocyte-macrophage cells, and it inhibited the dimethyl sulfoxide (DMSO)-induced differentiation of Friend murine erythroleukemia cells (FLC) at levels between 10(-10) and 10(-12) mol/L.

Characterization of a novel erythropoiesis-inhibiting human protein.

We have isolated an erythropoiesis-inhibiting protein, DIP (differentiation-inhibiting protein), from the blood of a 60-year-old woman suffering from pure red cell aplasia. This protein inhibits the growth and differentiation of normal human and murine BFU-E, but not CFU-E, cells as well as dimethyl sulfoxide-induced hemoglobin synthesis by Friend murine erythroleukemia cells. It appears that DIP primarily affects differentiation rather than proliferation, because it does not inhibit the proliferation of untreated Friend erythroleukemia cells.

Potential therapeutic role of cisplatinum in autologous bone marrow transplantation: in vitro eradication of neuroblastoma cells from bone marrow.

Cisplatinum may prove to be a valuable agent for the elimination of diseased cells in the bone marrow of patients with neuroblastoma. In this study, we measured the efficacy of cisplatinum on human neuroblastoma cell lines and on normal human bone marrow progenitors, GM-CFC and CFU-F. Data indicate that the therapeutic index of cisplatinum is high.

Autocrine differentiation-inhibiting factor (ADIF) from chicken erythroleukemia cells acts on human and mouse early BFU-E erythroid progenitors.

tsAEV-LSCC HD3 chicken erythroid cells transformed by the avian erythroblastosis virus (AEV) secrete an autocrine differentiation-inhibiting factor, ADIF, which blocks differentiation without affecting proliferation of the chicken erythroid cells that synthesize and secrete it into the culture medium. The chicken erythroleukemia cell ADIF activity is not restricted to avians. It prevents dimethylsulfoxide (DMSO) from stimulating murine Friend erythroleukemia cells to synthesize hemoglobin.

Granulopoietic differentiation in long-term bone marrow cultures from children with congenital neutropenia.

The capacity of granulopoietic precursor cells (CFU-GM) to differentiate in vitro was evaluated in five children with congenital neutropenia using short-term colony assays and long-term marrow cultures. In all five children, methylcellulose assays revealed normal numbers of CFU-GM, which displayed an appropriate response to various sources of GM-CSF and differentiated up to the polymorphonuclear leukocyte state (PMN). In contrast, neutrophil PMN were not observed in long-term bone marrow cultures from three patients, despite a normal production of CFU-GM, myeloblasts, and promyelocytes during the 5-6 week culture period.

Normal human serum-stimulating activity on granulocyte-macrophage colony formation in vitro.

The action of human serum on granulocyte-macrophage progenitors (CFC-gm) from normal human bone marrow has been studied. When human serum was added to a culture of nonadherent bone marrow cells, no colony formation was observed in the absence of exogenous colony-stimulating factor (CSF); however, the number of colonies increased with the addition of exogenous CSF. When serum was added to a culture of unseparated bone marrow buffy coat cells, colony formation appeared even in the absence of exogenous CSF.

Erythropoietic recovery in human after extended field radiotherapy. Ferrokinetic studies of patients treated by radiotherapy followed by autologous bone marrow transplantation and of patients treated by moderate doses (20 Gy) of radiotherapy.

The ability of human irradiated bone marrow to provide suitable environment for migrating stem cells has been studied in four patients. These had received chemotherapy plus doses of 40 Gy to thoracic vertebrae and sternum, followed by autologous bone marrow transplantation. The erythropoietic activity in the non-irradiated areas was increased but it was low in irradiated areas at 3.

Preliminary results in secondary acute non-lymphocytic leukemia (ANLL) treated with Idarubicin.

The results of Idarubicin treatment in patients with secondary acute non-lymphocytic leukemia are presented: 7 courses have been performed in 6 patients and 4 complete remissions have been induced in three of them. Tolerance was excellent and no cardiotoxicity was observed. However, remissions were short and combination therapy is suggested.

Late effects on human bone marrow after extended field radiotherapy.

Thirty-two patients with lymphoma were treated with extended radiotherapy (RT) at a dose of Gy and were studied by ferrokinetic studies and surface counting at various times following irradiation. Loss of hematopoietic activity in the irradiated areas is compensated by increased activity in the non-irradiated areas. Despite the return of peripheral blood counts to normal, the hyperactivity of the non-irradiated bone marrow persists over up to 13 years after RT, while the hematopoietic activity of the irradiated areas remains depressed and is only slightly higher than immediately after RT.

[Granulocyte progenitor cells (CFC) culture in the adult chronic idiopathic neutropenia. A study of 12 cases (author's transl)].

Granulocyte progenitors (CFC) from 12 patients with idiopathic neutropenia were cultured in vitro and followed, in some cases, for several months. The results were similar whatever the degree of neutropenia and in the presence or absence of medullary hypoplasia. The medullary concentration of CFC was always clearly depressed, which correlated with a very low total number of CFC.

Methylcellulose culture of human granulocytic progenitor cells (CFC *): results of bone marrow and blood cultures for normal subjects.

Normal values for the colony-forming ability of granulocytic progenitor cells (CFC) were established for 26 samples of normal bone marrow and 8 samples of normal blood cultured in methylcellulose. The concentration of CFC in the marrow was measured classically as the number of CFC per 10(5) nucleated marrow cells plated and, in addition, as the number of CFC per 10(5) precursors (myeloblasts, promyelocytes, and myelocytes) and per 10(5) metamyelocytes. A value approximating the total number of marrow CFC was calculated by using the number of CFC per 10(5) metamyelocytes.

In vitro medullary granulocytic progenitor (CFUc) cultures from 6 cases of granulocytopenias.

Medullary granulocyte progenitor (CFUc) cultures were grown in vitro from samples taken from 6 patients with toxic granulocytopenia caused by either thiamphenicol cephalothin or amidopyrine and who are now apparently cured. A decreased in the medullary concentration of CFUc has been observed and a calculated estimate shows that there was a decrease in their absolute number. A decrease in the number of CFUc per 10(5) metamyelocytes suggests a possible compensation by mitotic amplification between the stem cell and the differentiated cells.

Effects of treatment of malignant lymphomas on the granulocytic progenitor cells (CFUc).

The goal of this work was to appraise the after-effects of radiotherapy and associated radio- and chemotherapy on hematosarcomas by studying the granulocytic progenitor cells (CFUc). The bone marrow of 14 subjects was cultured in methylcellulose 1--6.5 years after completion of radiotherapy.

[Interest of sequential "in vitro" cultures of granulomonocytic stem cells (CFUc) in the management of chemotherapy in a case of multiple myeloma (author's transl)].

Sequential measures of granulomonocytic stem cell (CFUc) pool were undertaken during chemotherapy in a case of multiple myeloma. Whereas the number of blood granulocytes remained unchanged, the total number of CFUc was markedly decreased. Therefore the CFUc marrow pool can be considered as one of the data in the management of chemotherapy.

Comparative study of 111In and 59Fe bone marrow scanning.

The aim of this work is to examine the relative merits of 59Fe and 111In scanning in estimating the functional value of the various erythropoietic areas and in appraising bone marrow distribution and extension. At first we studied a group of patients with heterogeneous distribution of bone marrow secondary to irradiation, ferrokinetics serving a reference for the comparison of 111In and 59Fe scanning. The functional value fo 59Fe scanning was thus proved, in contrast to 111In scanning which was erroneous for 13 of the 29 bone marrow areas studied.

[In vitro granulocyte colony formation in children with neuroblastoma (author's transl)].

In vitro granulocyte colony formation has been studied using the methylcellulose system in 22 children with neuroblastoma, 13 of them having bone marrow invasion. Only one third exhibited normal results. There were various disturbances of granulopoiesis in vitro: colony forming cells were decreased or increased and in the amplification compartment either an ineffective leucopoiesis or an increase in the number of mitosis was present.

[Granulocyte stem cells in a case of Chediak-Higashi-Steinbrinck syndrome].

Bone marrow from a child with Chediak-Higashi-Steinbrinck disease was cultured. It was found that all cells with granulocytic colony forming ability were affected by the disease. Cytoplasmic vacuoles were identified as lysosomes by their cytochemical staining.