Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of purified 125I-labeled murine granulocyte colony stimulating factor (125I-G-CSF) to normal and leukemic human cells was examined. Normal neutrophils and their precursors demonstrated specific labeling with 125I-G-CSF, whereas eosinophils, lymphocytes, and erythroid cells did not. Normal human promyelocytes demonstrated the highest binding among hemopoietic cells. Human myeloid leukemic cells also demonstrated consistent specific labeling with 125I-G-CSF. Normal promyelocytes and chronic myeloid leukemia promyelocytes demonstrated only transient clonal proliferation in vitro when stimulated by G-CSF, but this was not always the case with acute promyelocytic leukemic cells. The qualitative responsiveness of normal and leukemic cells to G-CSF was very similar despite heterogeneity in receptor numbers on individual cells. A subset of acute promyelocytic leukemic cells appeared unresponsive to stimulation by GM-CSF.
 ...
PMID:Binding characteristics and proliferative action of purified granulocyte colony-stimulating factor (G-CSF) on normal and leukemic human promyelocytes. 244 1

Human peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers gave rise to three types of colonies that could be distinguished by their unique morphological characteristics; 5.1 +/- 0.9 (mean +/- SE) loose colonies of small cells, 2.1 +/- 0.9 packed colonies of larger cells, and 1.6 +/- 0.7 mixed colonies, were formed when PBMC (2 x 10(5) cells/dish) from 10 healthy volunteers were cultured in the medium containing methylcellulose. Cytochemical analysis with Astra blue-eosin dual staining revealed that all types of colonies consisted of various proportions of basophils, eosinophils, and hybrid (eosinophilic and basophilic) granulocytes which contained both of granules. These hybrid granulocytes were also identified by the ultrastructural features of two kinds of the granules. Relationships between cell numbers added to culture and formed colony numbers indicated colony of the cells to form the colonies. The colonies formed from untreated patients with chronic myelogenous leukemia (CML) during chronic phase were sevenfold of those from healthy volunteers. The colonies formed from treated patients with CML were normal in number. The number was 40 times greater in culture from a patient with basophilic crisis and a patient with myeloid crisis than normal, whereas that from a patient with lymphoid crisis were within normal limit. The number of the colonies from PBMC of patients with eosinophilia were in normal range, whereas those from bone marrow were six times or more than those from PBMC. These findings suggest that PBMC contains common basophil-eosinophil progenitors, and the culture used in this study in considered to be useful in the examination of basophil and eosinophil production from PBMC. Further studies using more purified cell population and other sources of colony stimulating factors such as interleukin-3 (IL-3), IL-4, IL-5, and granulocyte-macrophage colony stimulating factor should be carried out in order to clarify the significance of hybrid granulocytes in basophil and eosinophil proliferation and differentiation.
 ...
PMID:[Studies on human basophil and eosinophil colonies in human blood mononuclear cell culture: presence of common basophil-eosinophil progenitors]. 248 Mar 21

We have analyzed the ability of highly purified preparations of human NK cells to produce CSF. NK cells, purified by negative selection from 10-d cultures of PBMC incubated with irradiated B-lymphoblastoid cell lines, were stimulated with rIL-2, FcR(CD16) ligands (particulate immune complexes or anti-CD16 antibodies bound to Sepharose), a combination of CD16 ligands and rIL-2, or the phorbol diester phorbol dibutyrate (PDBu) together with the Ca2+ ionophore A23187. Both rIL-2 and CD16 ligands induce accumulation of GM-CSF mRNA in NK cells and the combined effect of the two stimuli is synergistic. Maximal accumulation of GM-CSF mRNA is observed after PDBu/A23187 stimulation. The participation of contaminant T cells in the observed expression of the GM-CSF gene is excluded because CD16 ligands do not stimulate T cells and CD3 ligands, powerful stimulators of T cells, are inactive on NK cells. Accumulation of CSF-1 mRNA is observed only in NK cells stimulated with both CD16 ligands and rIL-2, whereas accumulation of IL-3 mRNA is observed only in NK cells stimulated with PDBu/A23187. Transcripts of the G-CSF, IL-1 alpha, and IL-1 beta genes were never detected in NK cells in these experiments. The kinetics of accumulation of GM-CSF and CSF-1 mRNA in NK cells stimulated with CD16 ligands and rIL-2 peaked at 2-4 h and was slower than that of TNF and IFN-gamma mRNA, which peak at 1 h. GM-CSF was precipitated from the supernatant fluids of NK cells stimulated with PDBu/A23187 and its biological activity was demonstrated by the ability of the supernatants to sustain proliferation of the TALL-101 cell line or CML blasts. Biological activity of IL-3 and CSF-1 was demonstrable in supernatant fluids of NK cells stimulated with PDBu/A23187 and CD16 ligands/rIL-2, respectively.
 ...
PMID:Production of hematopoietic colony-stimulating factors by human natural killer cells. 252 57

We describe here the presence of two classes of binding sites for GM-CSF expressed on blasts freshly isolated from five AML patients and one patient with CML in blastic phase: one of high-affinity (38-177 per cell, KD 8-150 pM) and one of low-affinity (121-806 per cell, KD 503-2683 pM). No correlation is observed between the receptor number, receptor affinity, and the growth stimulatory effect of GM-CSF on leukemic blast progenitors. Blasts from two cases showed no or negligible response to GM-CSF but expressed comparable numbers of receptors when compared with the numbers expressed by the sensitive blasts. Our data suggest that significant proliferative effects of GM-CSF can occur at low levels of high-affinity receptor occupancy. Lack of responsiveness to GM-CSF in some AML patients is not correlated to the absence of GM-CSF receptors on leukemic cells. Reduction in the growth of blast progenitors at high concentrations of GM-CSF may be attributed to the differentiating activity of GM-CSF via low-affinity receptors on leukemic cells.
 ...
PMID:Specific binding of radioiodinated human GM-CSF to the blast cells of acute myeloblastic leukemia. 254 43

Treatment with GM-CSF or G-CSF is becoming widely used in patients with chronic neutropenia, or who are aplastic following chemotherapy or autologous or allogeneic bone marrow transplantation. Recently, some authors have described a phenomenon analogous to cyclic agranulocytosis following treatment with G-CSF in a patient with chronic neutropenia. We wish to describe the same phenomenon in a patient with chronic granulocytic leukemia who received GM-CSF (Sandoz) after T cell depletion in order to accelerate hematological reconstitution.
 ...
PMID:Transient cyclic neutropenia following GM-CSF in a patient with chronic granulocytic leukemia transplanted with HLA-identical T cell-depleted donor bone marrow. 267 45

Juvenile chronic myelogenous leukemia (JCML) is a rare myeloproliferative disorder of early childhood that is clinically and cytogenically distinct from the well-recognized adult type of chronic myeloid leukemia. Unlike the adult disease, growth of hematopoietic progenitors from peripheral blood (PB) occurs in the absence of exogenous stimulus even at low cell densities. This so-called "spontaneous" growth can be abrogated by adherent cell depletion and appears to depend on production of endogenous growth factors. We studied seven children with JCML to determine the nature of endogenous stimulators. With isolated PB mononuclear cells (PBMNCs) and a 3H-thymidine (3H-TdR) incorporation assay, JCML cells were shown to incorporate high levels of 3H-TdR when cultured in the absence of stimulus even at low cell densities. When neutralizing antisera prepared against each of the four known colony-stimulating factors (CSFs), GM-CSF, G-CSF, M-CSF, and interleukin-3 (IL-3), as well as antisera against interleukin-1 (alpha and beta) and tumor necrosis factor (TNF) were added to these cultures, only the antisera against recombinant human GM-CSF (rhGM-CSF) consistently resulted in significant inhibition of cell proliferation, achieving up to 72% inhibition of 3H-TdR incorporation in one case. Monoclonal antibodies (MoAbs) against rhGM-CSF resulted in a similar and highly significant degree of inhibition. A marked inhibitory effect of rhGM-CSF antiserum on "spontaneous" growth of PB CFU-GM derived colonies in semisolid medium was also demonstrated in four of five patients studied (87% to 90% inhibition). Production of growth factors by highly enriched JCML monocytes was variable. When initially studied in five of the seven patients, the monocytes from three of the patients revealed increased release of IL-1-like activities; two patients had levels similar to those of controls. One patient with normal levels when initially studied was later shown to have markedly increased amounts of IL-1-like activities in a second preparation of monocyte-conditioned medium (MCM). High levels of GM-CSF were detected in the initial MCM from one patient, but this may have indirectly reflected elevated IL-1-like activities present in the MCM. IL-3 and M-CSF levels were either low or undetectable in the patients studied as compared with MCM prepared with normal adult monocytes. These results clearly implicate GM-CSF as the primary endogenous regulator of JCML cell proliferation in culture and suggest that this malignant myeloproliferative disease may in part result from paracrine stimulation of marrow progenitor cells by growth factors/cytokines secreted by the malignant monocytes.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor is an endogenous regulator of cell proliferation in juvenile chronic myelogenous leukemia. 267 15

PGM-1 is a transplantable leukemia of C3H/HeJ mice growing as a population of undifferentiated blast cells with a predisposition to form subcutaneous tumors and to grow in lymphoid organs. Cell survival and proliferation in vitro are absolutely dependent on stimulation by hemopoietic growth factors, and up to 100% of tumor cells can form colonies of mature granulocytes and/or macrophages in semisolid cultures, the colonies containing no clonogenic cells. Most clonogenic cells in the leukemic population respond to stimulation by multi-colony-stimulating factor (IL-3) or GM-CSF, but some respond also to M-CSF, G-CSF, IL-4, IL-5, or IL-6. In their surface phenotype and proliferative characteristics in vitro, PGM-1 leukemic cells resemble normal granulocyte-macrophage progenitor cells, and the leukemia may be a useful model for human chronic myeloid leukemia.
 ...
PMID:PGM-1: a transplantable murine leukemia of granulocyte-macrophage progenitor cells. 268 46

A great deal of information has emerged over the past decade regarding the gene structures and corresponding protein products of the cellular and transformation-associated forms of the ABL tyrosine kinase family. Many reports have also detailed the biological effects of these proteins (particularly the viral ABL forms) on a broad range of cell types. However, in spite of all these research efforts, the precise role of the ABL gene in normal and neoplastic growth remains to be determined. To elucidate the mechanism of action of normal and altered ABL proteins, it is imperative to identify their relevant cellular substrates and establish the role of the ABL target proteins in transformation and normal cellular growth. The availability of temperature-sensitive ABL proteins, coupled with the use of sensitive anti-phosphotyrosine antibodies, should be useful in this respect. Purification of enzymatically active, intact forms of the ABL proteins produced in insect cells by employing baculovirus expression vectors should permit direct comparison of the biochemical properties and tertiary structures of the various members of the ABL protein kinase family. Such studies will aid in understanding the nature of the alteration of ABL which results in the activation of its transforming potential. Furthermore, the availability of purified ABL proteins should permit examination of interactions of ABL with other growth-regulatory proteins, such as growth factor receptors. It has been shown that transformation-associated ABL proteins interact with the IL-3, IL-2 and GM-CSF growth-factor pathways. These and other components of the cellular signalling pathways are potential ABL targets. The elucidation of ABL function by a variety of approaches such as those described above will ultimately aid in the development of far-reaching therapeutic treatments for at least two forms of human leukaemia: Ph positive CML and Ph positive ALL.
 ...
PMID:Role of the ABL oncogene tyrosine kinase activity in human leukaemia. 333 51

A patient with an unusually prolonged course of Ph' positive chronic myeloid leukemia is presented. His disease was marked by cyclic leukocytosis, various chromosomal aberrations and secondary thrombasthenia. In vitro culture studies and granulocyte-macrophage colony stimulating factor (GM-CSF) production were consistent with responsiveness of the leukemic clone to GM-CSF. The possible relationship between the long survival and the feedback regulation of leukopoiesis is raised.
 ...
PMID:Cyclic leukocytosis and long survival in chronic myeloid leukemia. 640 19

The effect of basic and acidic fibroblast growth factors on leukemic blast progenitors was studied in 14 patients with acute myelogenous leukemia and in one patient with chronic myelocytic leukemia in myeloid crisis. bFGF and aFGF stimulated blast-colony formation by leukemic blast progenitors cultured in methylcellulose in two patients. In the other 13 patients, no significant effect of either FGF on blast-colony formation was noted. The combination of bFGF or a FGF and G-CSF, GM-CSF, interleukin-3, or stem cell factor (SCF) had a synergistic effect on blast-colony formation in three patients. In the other patients, however, synergism between FGF and CSF was not detected. In fact, bFGF was found to suppress the stimulation of blast-colony formation due to GM-CSF in one of 10 patients and that due to SCF in four of eight patients. aFGF suppressed the stimulation of blast-colony formation due to GM-CSF in two of 11 patients and that due to SCF in four of eight patients. The results show that bFGF and aFGF do not directly play a major role in leukemic hematopoiesis but that they may modulate the cytokine network affecting leukemic cell growth.
 ...
PMID:The effect of basic and acidic fibroblast growth factors (bFGF and aFGF) on the growth of leukemic blast progenitors in acute myelogenous leukemia. 754 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>