Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herbimycin A, a selective inhibitor of tyrosine kinase activity, induced differentiation of leukemia cells isolated from Philadelphia chromosome-positive chronic myelogenous leukemia patients. However, it did not induce differentiation of leukemia cells from acute myelogenous leukemia patients, although these cells could be induced to differentiate by treatment with appropriate compounds. A selective inhibitor of tyrosine kinase might be useful in chemotherapy of Philadelphia chromosome-positive leukemia.
 ...
PMID:Control of growth and differentiation of Philadelphia chromosome-positive leukemia cells by tyrosine kinase inhibitors. 130 24

CD34 is a 115-kDa transmembrane glycoprotein of unknown function that is expressed on human hematopoietic progenitor cells and the small vessel endothelium of a variety of tissues. We have isolated a CD34 cDNA clone from a KG-1 cell library following three rounds of transient expression in COS cells and enrichment by panning with the anti-CD34 mAb MY10 and BI-3C5. The 5' and 3' ends of the full-length cDNA were subsequently amplified by polymerase chain reaction from KG-1 RNA; the final cDNA clone contained 2615 bp and ended in a poly(A) tail. COS cells transfected with the cDNA clone expressed a surface protein of approximately 110 kDa that was immunoprecipitated by MY10. Southern blot analysis suggested that CD34 is a single copy gene. A 2.7-kb CD34 transcript was observed in the hematopoietic cell lines KG-1, KMT-2, AML-1, RPMI 8402, and MOLT 13 and the endothelial cells BAE and EAhy926, but not in monocytes, resting T cells, or the cell lines Laz 509, HL-60, U937, K562, and HeLa. The cDNA sequence predicts a 40-kDa type I integral membrane protein with nine potential N-linked and numerous potential O-linked glycosylation sites in its extracellular domain. There are two consensus protein kinase C phosphorylation sites and one potential tyrosine kinase phosphorylation site in the cytoplasmic portion of CD34. CD34 has no significant sequence homology to any known protein but has some structural similarities to the heavily glycosylated leukocyte surface molecule CD43.
 ...
PMID:Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells. 137 Jan 71

In an effort to identify unique tyrosine kinases found in human leukemia cell lines, we utilized polymerase chain reaction (PCR) technology and degenerate oligonucleotide primers to produce a cDNA library of kinase catalytic domains found in the human monocytic cell line AML-193. This search yielded a member of the class 3 tyrosine kinases closely related to the murine kinase FD-22. Previous work has identified this kinase as JAK1. This class of tyrosine kinases is characterized by being ubiquitously expressed, lacking both a ligand-binding domain and a SH2 domain, while containing a second domain similar to a degenerate kinase domain. Our studies focused on the further characterization of this class 3 tyrosine kinase using Northern blot analysis to demonstrate an increase in steady-state mRNA by interferon-gamma in human monocytes. A human-hamster somatic cell hybrid panel and linkage mapping was used to assign JAK1 (aml-116) to human chromosome 1.
 ...
PMID:Characterization of a class 3 tyrosine kinase. 137 77

In the present study fresh leukemic cells obtained from 23 patients with acute myeloid leukemia (AML; FAB subtypes: three M1, five M2, two M3, five M4, eight M5) were investigated for the membrane expression of the CD4 molecule by cytofluorimetric analysis with an anti-CD4 monoclonal antibody (mAb). In 15 cases the presence of the CD4 mRNA was also investigated using Northern blot analysis. Membrane expression of the CD4 molecule was demonstrated in 19 out of 23 cases, and it was found to be weaker than in CD4+ lymphocytes and monocytes obtained from normal controls. Full-length CD4 mRNA was detected in 12 out of 15 (80%) cases, and AML cells positive for CD4 mRNA expression also expressed the CD4 antigen. Since the CD4 molecule expressed by T cells is associated with p56lck, a member of the src family of intracellular tyrosine kinases, we investigated whether the CD4 molecule expressed by myeloid blasts is also associated with a tyrosine kinase activity. In vitro kinase assays performed on anti-CD4 immunoprecipitates from lysates of myeloid leukemia cells from four CD4+ cases were negative for the presence of a tyrosine kinase activity. This finding was not due to the lack of expression of members of the src family since we were able to detect at least p60src and p59fyn in myeloid leukemia cells. According to our results, the CD4 molecule seems to belong to the phenotypic repertoire of most AML, irrespective of their FAB subtypes. However, in myeloid blasts this molecule is not associated with a tyrosine kinase activity as it occurs in T lymphocytes.
 ...
PMID:The CD4 molecule belongs to the phenotypic repertoire of most cases of acute myeloid leukemia. 145 71

The activation of protooncogenes (ras, fms and myc genes) by point mutations in hematological malignancies are described in this review. Ras mutations are found in a variety of human malignancies at codon 12, 13, and 61. Generally, N-ras mutations are frequent in hematological malignancies. Fms mutation at codon 301 and 969, which are seen in 10 to 20% cases of AML and MDS, increase tyrosine kinase activity of the fms products. Ras and fms mutations are postulated to influence leukemogenesis at rather early stages. Burkitt lymphomas are characterized by specific chromosomal translocations between c-myc gene and one of the immunoglobulin genes. Furthermore, mutations in the 3' border of the exon 1 of c-myc are frequent, and may play an additional role in pathogenesis of Burkitt lymphoma.
 ...
PMID:[Activation of protooncogenes by point mutations in hematological malignancies]. 151 54

Tyrosine protein kinases (TPK) help regulate cellular growth and differentiation. Several proto-oncogenes encode for protein products with associated tyrosine kinase activity. An assay for TPK activity was performed in cell extracts using a synthetic peptide substrate and [32P] adenosine triphosphate (ATP). TPK activity was elevated in K-562 cells, which possess an amplified c-abl oncogene, compared to normal blood mononuclear cells (K-562 = 9.37 +/- 1.72 [mean +/- standard deviation] pmol ATP/10(6) cells/min; normal = 1.14 +/- 0.46, p less than 0.01). TPK activity was measured in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL), myelomonocytic leukemia (MOL), acute myeloblastic leukemia (AML), and chronic lymphocytic leukemia (CLL). In patients with clinically active disease, elevated TPK activity was measured in mononuclear cells from five HCL patients (range 3.76-24.15) and from seven MOL patients. These elevated levels appeared to parallel disease activity, as low levels of TPK activity were measured in patients with inactive (treated) disease. Low levels of TPK were measured in mononuclear cells from active AML and CLL patients. Elevated TPK levels in patients with HCL and MOL may reflect the overexpression of a proto-oncogene or increased growth factor activity in immature or rapidly dividing leukemic cells. Serial TPK levels in HCL and MOL patients correlated with change in disease activity.
 ...
PMID:Increased tyrosine protein kinase activity in hairy cell and monocytic leukemias. 160 67

The c-kit proto-oncogene encodes a 145- to 160-Kd transmembrane tyrosine kinase, which is a member of the platelet-derived growth factor receptor family and is allelic with the murine white spotting locus (W). W mutations affect several aspects of hematopoiesis, most notably erythroid progenitors and mast cells. A monoclonal antibody, YB5.B8, had been raised against the leukemic blasts of a patient with M1-type acute myelocytic leukemia (AML) and it precipitates a 150-Kd cell surface glycoprotein from leukemic cells. The YB5.B8 epitope is expressed on mast cells, on up to 3% of normal mononuclear bone marrow cells, and it identifies a sub-group of AML patients with a poor prognosis. In view of similarities noted between the cell surface antigen identified by YB5.B8 and the c-kit protein product, we performed experiments to determine whether they are identical. c-kit RNA expression in the cell lines HEL (human erythroleukemia) and A172 (glioblastoma) was shown to parallel the expression of the YB5.B8 epitope in these lines as measured by flow cytometry. Immunoprecipitation analysis with anti-kit serum and YB5.B8 antibody indicated that the two antibodies identified proteins of identical size in HEL (155 Kd) and A172 (145 Kd) cells, and sequential immunoprecipitations with the kit and the YB5.B8 antibodies demonstrated that the two antibodies recognize the same molecule. The proteins identified by both the anti-kit and YB5.B8 antibodies displayed in vitro autophosphorylation activity in immune complex kinase assays. In addition, YB5.B8 was able to inhibit the binding of the kit ligand to HEL cells. These studies provide evidence that the YB5.B8 antigen and the c-kit protein product are identical and raise certain hypotheses regarding the role of c-kit in AML.
 ...
PMID:Monoclonal antibody YB5.B8 identifies the human c-kit protein product. 170 91

The c-kit proto-oncogene encodes a transmembrane receptor with a tyrosine kinase internal domain. C-kit has been mapped to the W locus in the mouse, and the gene encoding the ligand has been shown to be the product of the murine SI locus. Previous genetic studies have shown that the murine W and SI loci play important roles in the normal function of hemopoietic stem cells. As these stem cells have been identified as the origins of abnormal clones in acute myeloblastic leukemia (AML), a study was begun of c-kit in AML. By Northern blot analysis, it was shown that all of 21 blast populations from AML patients were kit expression positive, but some AML cell lines did not transcribe detectable c-kit mRNA. This study is now extended to the responses of freshly obtained AML cells and cell lines to the ligand, mast-cell growth factor (MGF). In culture, fresh cells usually responded to added ligand with increases in both self-renewal and terminal divisions. The most obvious effects were seen when MGF was combined with either IL-3 or G-CSF. The response of cell lines to MGF mirrored their expression of c-kit; expression positive lines responded in culture with patterns similar to those seen for fresh cells. C-kit expression negative cells did not respond to MGF. RNA prepared from the cells giving rise to one such line, OCI/AML-5, was available for study. mRNA for c-kit could not be detected in this RNA sample by Northern blot analysis or the polymerase chain reaction. Thus the heterogeneity found in AML blast populations extends to the involvement of c-kit and its ligand in growth regulation, although blast populations without this regulatory apparatus appear to be rare.
 ...
PMID:Mast cell growth factor, a ligand for the receptor encoded by c-kit, affects the growth in culture of the blast cells of acute myeloblastic leukemia. 171 40

The c-kit proto-oncogene product is a member of the family of growth factor receptors with intrinsic tyrosine kinase activity. In the mouse c-kit maps to the W locus, which is known to be of central importance in hematopoiesis. Monoclonal antibody (MoAb) YB5.B8, which was raised against peripheral blood blast cells from a patient with acute myeloid leukemia (AML), was recently shown to bind to the extracellular domain of the c-kit product. This antibody does not bind detectably to normal peripheral blood cells and identifies a sub-group of AML patients with poor prognosis. We have used MoAb YB5.B8 to study the expression of c-kit by normal human bone marrow cells by immunofluorescence and flow cytometry, and to isolate multipotential and erythroid colony-forming cells. In a series of 11 normal adult bone marrow specimens, MoAb YB5.B8 bound to 4.0% +/- 1.8% of the cells in the low-density fraction. Dual-labeling experiments were performed with YB5.B8, and CD33, CD34, and CD10 MoAbs. Three populations of cells binding YB5.B8 could be identified based on their pattern of coexpression of the other markers; ie, YB5.B8+/CD34+/CD33-, YB5.B8+/CD34+/CD33+ and YB5.B8+/CD34+/CD33+. These populations had distinctive two-dimensional light scatter characteristics and are likely to correspond to precursor colony-forming cells, colony-forming cells, and maturing mast cells, respectively. No cells binding both YB5.B8 and an MoAb to the early lymphoid marker CD10 were found, implying that most early lymphoid cells do not express c-kit. MoAbs to the c-kit protein should prove valuable in multimarker studies of human hematopoietic stem and progenitor cells. Definition of a reference range of c-kit expression in normal human bone marrow will provide a sound basis for further studies of this marker in diagnosis and prognosis in AML.
 ...
PMID:Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow. 171 44

Myeloid leukemic progenitor cells proliferate in vitro in response to a variety of humoral factors, the most prominent among these being granulocyte-macrophage colony-stimulating factor (GM-CSF). The mechanism by which GM-CSF transduces its proliferative signal in acute myeloid leukemia has been extensively investigated over the past year. It is now known that the GM-CSF belongs to a new family of hematopoietic growth factor binding proteins which are characterized by a relatively short intracytoplasmic domain that lacks a tyrosine kinase sequence. Nevertheless, studies performed using GM-CSF-dependent leukemic cell lines demonstrate the appearance of several new phosphotyrosine species after GM-CSF exposure, suggesting that receptor activation is directly or indirectly linked to tyrosine kinase stimulation. Apart from the basic biology of GM-CSF-induced signal transduction, the ability of this factor to enhance the S-phase fraction of myeloid leukemia blasts may have important therapeutic implications. Clinical trials are currently being conducted in an attempt to determine whether GM-CSF is able to overcome kinetic resistance of leukemic myeloblasts to cell cycle-specific agents such as cytarabine in the treatment of patients with acute myeloid leukemia.
 ...
PMID:Growth regulation of malignant clonogenic cells in acute myeloid leukemia. 182 75


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