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)

Humanized IgG1 M195 (HuG1-M195), a complementarity determining region-grafted recombinant monoclonal antibody, is reactive with CD33, an antigen expressed on myelogenous leukemia cells. M195 is in use in trials for the therapy of acute myelogenous leukemia. Since biological activity of IgG may depend, in part, on multimeric Fab and Fc clustering, homodimeric forms of HuG1-M195 were constructed by introducing a mutation in the gamma 1 chain CH3 region gene to change a serine to a cysteine, allowing interchain disulfide bond formation at the COOH terminal of the IgG. Despite similar avidity, the homodimeric IgG showed a dramatic improvement in the ability to internalize and retain radioisotope in target leukemia cells. Moreover, homodimers were 100-fold more potent at complement-mediated leukemia cell killing and antibody-dependent cellular cytotoxicity using human effectors. Therefore, genetically engineered multimeric constructs of IgG may have advantages relative to those forms that are found naturally.
 ...
PMID:Engineered humanized dimeric forms of IgG are more effective antibodies. 140 60

The effects of two natural peptides, dolastatin 10 and dolastatin 15, on growth and differentiation of hematopoietic cells were studied using freshly explanted leukemia cells and continuous leukemia cell lines. The proliferation of several myeloid cell lines and of growth-factor-stimulated peripheral blood cells from patients with acute myeloid leukemia (AML) was efficiently inhibited by the two agents at concentrations between 1 and 0.01 nM. Growth inhibition was dose-dependent and reversible. Neither of the dolastatins exhibited significant cytotoxicity on dividing cells, nor did they interfere with the viability of resting cells. The 12-O-tetradecanoylphorbol 13-acetate or bryostatin I induced differentiation of AML cells was not affected by the dolastatins. Short-term exposure to the phorbol ester conferred reduced sensitivity of the cell line HL-60 to the antiproliferative effect of the drugs. Our data suggest that the dolastatins alone or in combination with other drugs could exert a role in the treatment of human myeloid leukemia.
 ...
PMID:Dolastatin 10 and dolastatin 15: effects of two natural peptides on growth and differentiation of leukemia cells. 140 59

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 ectopic expression of lineage markers on irrelevant cell types may be of importance in the differentiation pathway(s) of these cells. One example, that is the subject of this study, is the presence of the interleukin-4 (IL-4) receptor on the surface of the human HL-60 myeloid leukemia cell line. The presence of such a receptor, that at first seems to be a simple genetic misprogramming, has an unusual biological function: It serves as a bridge to link the B cell growth factor IL-4 in order to transduce a number of differentiation signals in this M2 acute myeloid leukemia (AML) population. Signal transduction is followed by stimulation of RNA synthesis and subsequent induction of differentiation. Daily administration of low IL-4 dose yields proliferative senescent cells that exhibit 66% of growth inhibition in a 5-day tritiated thymidine incorporation assay. These cells clearly exit from the standard M2 morphology and show more mature characteristics as assessed by the Giemsa-Wright staining technique, followed by a 2-fold increase of the monocyte-granulocyte-specific Mac-1 surface antigen. Cellular function is also affected positively since phagocytosis of latex beads increases considerably after IL-4 treatment. Finally, as reported for normal human and murine monocytes and macrophages, the receptor-ligand interaction augments the levels of the class I and class II antigenic determinants by approximately 60%. Our results suggest that ectopic expression of markers may be a "distinct" event required during a short period in the differentiation of certain hemopoietic cells leading to mature and normal phenotypes.
 ...
PMID:The role of IL-4 in human myeloid leukemia: stimulation of RNA synthesis and transduction of differentiation signals through an IL-4 receptor leads to functional and HLA positive HL-60 cells. 147 51

Erythroleukemia (EL) is a rare form of myelogenous leukemia the classification and definition of which has evolved over the course of its 80-year descriptive history. In 1976 the French American British (FAB) Cooperative Group included EL within the classification system of acute myelogenous leukemias as AML-M6, and agreed on a quantitative standard to be used in the diagnosis of this disorder. The standards were revised in 1985 to the form in use today. We selected a series of 15 cases from our records which specifically fit the FAB criteria for AML-M6. Extensive direct comparison between our series and the old literature is not practical because of the changes which have occurred in classification and definition of the disease. Overall we found a rough correlation between the clinical and laboratory data shown in the old literature on EL and data from our cases. These cases underscore characteristic laboratory features which correspond to what is now defined as AML-M6: these patients present with pancytopenia, frequent peripheral blood nRBCs and no, or few, peripheral blood blasts. In addition, we note the presence of a hybrid myeloid-erythroid blast in the bone marrow in this disease and suggest that this may be characteristic of this type of AML. Old literature on EL has generally shown it to be a disease of the elderly, yet we found a subset of younger patients whose clinical outcome was significantly better than that of the older patients. Finally, EL has historically been viewed as a disease in which patients progress from a prodrome through erythroleukemia to other acute myeloid leukemia (AML) subtypes. Consistent with this idea, half of our 15 patients had been previously diagnosed with myelodysplastic syndrome or received chemotherapy. On the other hand only one of the 15 patients converted to another type of AML during his course.
 ...
PMID:Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature. 148 89

10 patients between the ages of 5 and 40 yrs with myeloid leukemia (4 acute, 6 chronic) in early (5 cases) or intermediate stage of the disease were given Cyclophosphamide and Busulfan (6 cases) or Cyclophosphamide, Busulfan and VP-16 (4 cases with CML) and bone marrow transplants from HLA-matched donors (in 9 cases from siblings and in one case from HLA phenotypically matched father). There was one transplant related death and 3 relapses in CML cases. In cases which relapsed GvHD was not observed. Altogether acute GvH and chronic GvHD was seen in 2 and 4 cases, respectively. All grafted cases with AML survive in continuous remission lasting more than 2 years (median 30.5 month).
 ...
PMID:[Allogeneic bone marrow transplantation in myeloid leukemia: chemical conditioning, clinical course and results]. 148 72

Testicular relapse (TR) in adult acute myelogenous leukemia (AML) is uncommon, occurring in only 1-2% of patients with bone marrow relapse. TR in the absence of systemic relapse has been reported previously in 2 adults and 12 children, of which 67% were monocytic variants of AML. This article presents the case of a 29-year-old man with AML that relapsed in his testicle without evidence of bone marrow relapse. This patient and the two previously mentioned adults experienced bone marrow relapse within 2 months and died within 7 months of their TR. TR in adult myelogenous leukemia should be considered a harbinger of systemic relapse and suggests a need for aggressive local and systemic therapy.
 ...
PMID:Testicular relapse in adult acute myelogenous leukemia. 151 5

Plasmacytoid T-cell (PTC) lymphoma is a rare clinicopathologic entity characterized by generalized lymphadenopathy in association with a myeloproliferative disorder. Hepatosplenomegaly and weight loss frequently are present. Nodal T-zone expansion by mononuclear cells with ultrastructural and immunohistochemical features typical of PTC is diagnostic. All of the five previously reported cases of PTC lymphoma coincided with or heralded the onset of a clinically aggressive myeloid leukemia. This strong association and recent immunohistochemical findings in reactive or neoplastic PTC favored a monocyte/macrophage derivation of these cells, and it has been suggested that they be renamed plasmacytoid monocytes (PM). Two additional cases of PTC lymphoma were studied at the institutions of the authors, and the findings supported the concept that PTC belong to the monocytic lineage. The disease presentation was generalized lymphadenopathy with constitutional symptoms. One patient also had hepatosplenomegaly and bilateral renal enlargement concomitantly with myelofibrosis with myeloid metaplasia that progressed within months to acute myelogenous leukemia. Similar rapid evolution of acute monoblastic leukemia occurred in the other patient. Tumor cells within subtotally effaced lymph nodes had positive findings for CD45, CD4, CD7, and LN2 and negative findings for CD3, CD8, and beta F1. Occasional cells had positive findings for CD2. One case demonstrated CD5, HLA-DR, CD71, and CD43 (Leu-22)-positive cells. The myeloid/monocyte-associated antigens CD14 and CD68 were identified in both. The tumor cells lacked the B-cell markers LN1, CD20 (L26), CD19, and CD22 and did not rearrange immunoglobulin heavy chain genes and T-cell receptor beta, gamma, and delta chain genes. The term plasmacytoid T-zone lymphoma or PM proliferation is more appropriate for this rare disease. The close association of the PM proliferation with a myeloproliferative disorder indicates that the two entities are related.
 ...
PMID:Plasmacytoid monocyte proliferation associated with myeloproliferative disorders. 154 Aug 83

Existing in vitro culture technology does not permit the routine propagation of most human myeloid leukemias. Previous work has shown the usefulness of mice with severe combined immunodeficiency (SCID) for the growth of human lymphoblastic leukemia. We show here that human myeloid cell lines and bone marrow samples from patients with acute myeloid leukemia (AML) and blast crisis of chronic myeloid leukemia (CML) also grow in SCID mice. Human AML or CML cell lines (three of three lines tested) grew in the bone marrow and peripheral blood of the mice after intravenous (IV) inoculation in a pattern closely resembling human AML. To define the best conditions for the growth of primary human myeloid leukemia cells, samples were transplanted into mice at several alternative sites. Using flow cytometry and Southern analysis, mice were analyzed at defined intervals up to 36 weeks after transplantation for the presence of human cells in various tissues. For four of four patients with AML and two of two patients with blast crisis of CML, myeloblasts grew locally at the site of implantation and were detected in the murine hematopoietic tissues. In contrast, marrow implants from patients in the chronic phase of CML (six patients) showed infrequent and limited myeloid growth in the mice. These findings demonstrate that the SCID mouse is a reproducible system for the propagation of blastic human myeloid leukemias. The differential growth of early- versus late-phase CML suggests that the SCID mouse may be a useful assay for identifying biologically aggressive leukemias early in their clinical presentation.
 ...
PMID:Propagation of human blastic myeloid leukemias in the SCID mouse. 156 35

A human acute myelomonocytic leukemia cell line, KBM-3, was developed to study the pathophysiology of human acute myeloid leukemia. This cell line was characterized by morphology, immunophenotype, Giemsa-banding pattern, in vitro proliferation capacity, and tumorigenicity in nude mice. The KBM-3 cell line was established in the presence of exogenous lymphokines (human placenta-conditioned medium, HPCM), but medium for later passages did not contain HPCM. We found high cellular expression of the mRNA message for granulocyte-macrophage colony-stimulating factor (GM-CSF), which we suggest may be important for the immortalization of the cell line. KBM-3 cells have an immature myelomonocytic phenotype. Cytogenetic analysis revealed a pseudodiploid karyotype with five characteristic marker chromosomes and ranging in total number from 45 to 49. In suspension cultures, the cells had a doubling time of 23 h and a cloning efficiency of about 30% in soft agar independent of exogenous lymphokines. Two-thirds of nude mice injected with 1 x 10(4) KBM-3 cells and all animals injected with 1 x 10(5) cells developed S.C. granulocytic sarcomas within 6-8 weeks. These tumors were locally invasive but did not give rise to distant metastases. When transplanted to a new set of nude mice, all tumors formed secondary sarcomas at the site of implant. We conclude that the KBM-3 cell line may have value for studying the molecular events that underlie the neoplastic transformation in human myeloid leukemia.
 ...
PMID:KBM-3, an in vitro model of human acute myelomonocytic leukemia. 156 50


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