Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1988 and 1991, feline immunodeficiency virus (FIV) infection status was evaluated in 1,160 cats examined at an oncology referral and general practice in Los Angeles, California. Twenty-nine (2.5%) cats were FIV positive. Neoplasia was present in 18 of the 29 (62%) cats. Sampling for neoplasia was intentionally biased in the oncology referral group. However, 33% (6/18) of FIV-infected cats with neoplasia originated from the general practice. Three neoplastic processes were observed; myeloproliferative disease (MPD; 5/18), lymphoma (LSA; 5/18), and squamous cell carcinoma (SCC; 7/18). One cat had LSA and SCC. Extranodal sites of LSA were common (66%) in FIV-infected cats. Sites of LSA were submandibular and mesenteric lymph nodes, liver, kidneys, periorbital area, and diffuse (heart, pancreas, bladder). Sites of SCC were sublingual (n = 2), nasal planum (n = 3), nasal planum and eyelids (n = 1), and mandible (n = 2). Feline leukemia virus co-infection was observed in 17% (5/29) of FIV-infected cats. The FIV-infected cats with MPD were young (range, 8 months to 13 years; median, 4 years) and had short survival duration (2, 6, 21, 134, 249 days) even in response to aggressive treatment. The FIV-infected cats with LSA were older (median age, 8 years; range, 4 to 14 years) and survived 60 days if untreated. Cats administered chemotherapy survived 39, 45, 217, and 243 days; the latter 2 cats had partial remission of 2 months' duration. Older FIV-infected cats had SCC (median age, 12 years; remission range, 7 to 16 years) because of more frequent association of both diseases in older cats with outdoor environment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neoplasia associated with feline immunodeficiency virus infection in cats of southern California. 166 82

Restriction fragment length polymorphisms of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used to study clonality in peripheral blood leukocytes from 48 women with chronic myeloproliferative disorders (c-MPD). A total of 50% of patients were heterozygous for one or both of the polymorphic loci. These included 17 cases with polycythemia vera, four patients with essential thrombocythemia (ET), and three cases with idiopathic myelofibrosis (IMF). A clear-cut monoclonal X-inactivation pattern was observed in 17 of 24 cases including all IMF patients. Only one patient with PV exhibited a nonclonal composition of her leukocytes, while six cases demonstrated a predominantly clonal pattern in peripheral blood cells. Among the latter category reckoned three of four ET patients. Cell separation analyses were performed in one ET and three PV patients. In all four cases a monoclonal pattern of the granulocyte fraction could be established, while T lymphocytes of these patients were of nonclonal origin. These data suggest that the vast majority of c-MPDs arise from multipotent hematopoietic stem cells. Moreover, this type of clonal analysis might be of help in discriminating between primary MPD and reactive processes.
Leukemia 1990 Apr
PMID:Clonal analysis of chronic myeloproliferative disorders using X-linked DNA polymorphisms. 197 5

This thesis is a survey of nine previously published articles on MPO deficient PMN. The incidences in leukaemia and allied disorders of the presence of this abnormal subpopulation of mature neutrophils and the relationship to clinical course in AML, susceptibility to infections in AML, FAB classification in AML and MDS, cytogenetically defined aberrations in MDS and morphometrical characteristics were investigated. The aims of the studies were to examine the diagnostic as well as the prognostic value of the parameter, to examine the usefulness of the parameter as an predictive indicator of CR and relapse in AML and to examine the concept that MPO deficient PMN may originate from leukaemic precursors. MPO deficient PMN were found to occur in a minor number (less than 4% of the total number of PMN) in normal humans and the incidences of an abnormal number (greater than 4%) were found to be about 40% in AML (I, II, III, IV, VIII), 60% in CML (I, VII), 30% in MPD other than CML (VII) and 30% in MDS (V). The highest incidences in AML were found in the FAB subtypes possessing the most myeloid differentiation potential i.e. FAB M2 and FAB M4 (IV). In ALL, CLL, HCL, Hodgkin's disease, anaemia not related to leukaemia and leukaemoid reactions the incidences all were 0% (I, unpublished data). The abnormal MPO deficient PMN subpopulation, if present, disappeared when CR was achieved and reappeared when relapse eventually was developed (II, VIII). In both situations serial determinations showed that the change occurred before the usual routine blood examinations predicted CR and relapse; several days and several months prior, respectively (VIII). The probability of obtaining CR was lower in the AML patients with the abnormal subpopulation and the risk of developing relapse higher than in AML patients without the anomaly (II, VIII). These differences were not statistically significant, however. AML patients, showing an increased number of MPO deficient PMN, revealed a statistically significant increased susceptibility to infections (P less than 0.01) during the preremission phase accounting for 18% to 67% of the total number of infections in this period (III). This increase was positively correlated to the extent of the anomaly (P less than 0.002). The spontaneous occurrence of a subpopulation of MPO deficient PMN in MDS went together with a simultaneous progression in cytogenetically determined clonal chromosomal aberrations and were related to progression in FAB subtype as well (VI). Morphometrically MPO deficient PMN were characterized by a decreased total cell size and an increased nucleus size of the projected images (IX).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Myeloperoxidase deficient polymorphonuclear leucocytes in leukaemia and allied disorders. 285 15

By circumventing the need for metaphase preparations, fluorescent in situ hybridization (FISH) on interphase nuclei using chromosome-specific probes is a promising tool for the study of numerical chromosome aberrations not only in proliferating, but also in non-dividing cells. We analyzed 15 cases of monosomy-7-associated myeloid disorders with a biotinylated probe to the (peri)centromeric region of chromosome 7. Monosomy 7 was readily confirmed in all cases during active disease. In two patients only a minority of nuclei was monosomic, whereas cytogenetics had shown all metaphases to be missing one chromosome 7. FISH in one of them was able to identify a small marker chromosome as isolated pericentromeric region of chromosome 7. Minimal residual disease however could not be detected in three remission samples analyzed, as percentages of disomic nuclei were within the range of normal controls (96.8% 2.1%). In order to determine lineage involvement of the monosomic clone, a recent technique combining immunophenotyping and FISH (FICTION) was performed in one patient with AML after MPD. Monosomy 7 was found in virtually all myelomonocytic and erythroid cells (as discriminated by lineage-specific antibodies), in a part of CD34-positive precursor cells, but not in lymphocytes. We conclude that monosomy 7 in this patient is restricted to an early committed progenitor cell capable of erythroid and myelomonocytic differentiation.
Leukemia 1993 Mar
PMID:Interphase cytogenetics by fluorescent in situ hybridization (FISH) for characterization of monosomy-7-associated myeloid disorders. 844 44

One of the first known effects of the endogenous peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) is to inhibit entry into DNA synthesis of pluripotent haematopoietic stem cells (CFU-S) in mice. A specific anti-AcSDKP polyclonal antibody allows the level of the tetrapeptide by to be determined by enzyme immunoassay with good sensitivity and specificity. We present results demonstrating the presence of AcSDKP in humans: serum levels of 34 healthy controls were found to be between 0.7 and 2.5 pm/ml, regardless of age and sex. High levels were found in 44% of asymptomatic controls but only in 8% of AIDS patients out of a total of 37 patients with HIV. Subsequently, studies of serum levels were performed before treatment in 121 subjects with disorders of the nonlymphoid and the lymphoid lineages. Our results did not demonstrate any decrease in serum levels, however a moderate or marked increase was noted in one-third of the subjects, which was greater in disorders of the non-lymphoid lineages (48% of 72 patients) than the lymphoid lineage (21% of 50 patients). The most significant differences were observed between controls versus patients with myeloproliferative disorders (MPD, 24 patients: p < 0.001), controls versus patients with acute myelogenous leukaemia (AML, 15 patients: p < 0.02), as well as patients with AML versus patients with primary myelodysplastic syndromes (PMDS, 10 patients: p < 0.05). The pathophysiology of these abnormalities is discussed.
Leukemia 1993 Jun
PMID:Serum levels of a negative regulator of cell proliferation (AcSDKP) are increased in certain human haemopathies. 850 76

The expression of lymphoid-associated antigens (LAA) on blasts in acute myeloid leukemia (AML) and myeloproliferative disorders in myeloid blast crisis (MPD/MBC) has often been used to establish a diagnosis of acute mixed lineage leukemia (AMLL). The purpose of this study was to determine the incidence of LAA expression in AML and MPD/MBC (Ly + AML); to assess lymphoid differentiation at the genomic level in Ly + AML; and to compare features of Ly + AML with AML and MPD/MBC lacking these antigens (Ly-AML). Seventy-four consecutive cases of AML and MPD/MBC were reviewed for blast morphology, TdT reactivity, and cytochemistry results. Blast immunophenotyping was performed by multiparameter flow cytometry. Acute myeloid leukemia was subtyped according to the FAB classification. Acute myeloid leukemia and MPD/MBC cases expressing one or more of the following antigens, CD2, CD3, CD5, CD7, CD19, or CD20, were considered to be Ly + AML. Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement studies were performed by Southern blot analysis using probes for JH, Jkappa, and JBI/BII. Sixteen of the 74 cases (22%) were identified as Ly + AML. Of these, the T-cell-associated markers CD7, CD2, and CD5 were expressed on 7(44%), 6(38%), and 4(25%) Ly + AML cases, respectively. The B-cell-associated markers CD19 and CD20 were expressed on two cases (13%) and one (6%) case, respectively. The FAB subtypes were similarly represented among Ly + AML and Ly-AML. Expression of LAA did not correlate with TdT positivity. In nine cases of Ly + AML (7 expressing T-cell-associated antigens and two expressing B-cell-associated antigens), Southern blot analysis revealed no Ig or TCR gene rearrangements. These results suggest that expression of CD2, CD5, and CD7 in otherwise straightforward AML should not be taken as evidence of lymphoid lineage commitment and does not warrant a diagnosis of AMLL.
 ...
PMID:Lymphoid-associated antigen expression by acute myeloid leukemia. 871 71

Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, and 6-fluoromevalonate (Fmev), an inhibitor of diphosphomevalonate decarboxylase, blocked the synthesis of downstream mevalonate products, including prenyl-derived lipids, and prevented membrane localization of Ras in the myeloid cell line U-937. In contrast to lovastatin, which induced cytosol localization of Ras in U-937 cells, Fmev failed to increase cytosolic Ras and also completely prevented the proliferation of U-937 cells. Growth of U-937 cells was restored by the addition of lovastatin to Fmev-blocked cells. These results implied that a product of mevalonate metabolism proximal to isopentenyl diphosphate was responsible for the suppression of proliferation. To delineate the action of this endogenous inhibitor of cell proliferation and determine the relationship between its impact on Ras localization and cell proliferation, the effect of Fmev on a variety of leukemia- and lymphoma-derived cells was examined. Whereas Fmev blocked the growth of these cell lines, there were more than 50-fold differences in the concentrations required to inhibit the growth of individual cell lines by 90%. Regardless of its effect on cell proliferation, the biochemical effect of Fmev was similar. Thus, Fmev uniformly prevented the conversion of radiolabeled mevalonate to isopentenyl diphosphate and other downstream products, including synthesis of sterol and nonsterol lipids and prenylation of proteins. A correlation was noted between higher intrinsic rates of mevalonate synthesis by a cell and susceptibility to inhibition by Fmev. Thus, sensitivity of a cell line to inhibition by Fmev was associated with markedly increased rates of HMG CoA reductase activity that were further increased by incubation with Fmev. Whereas Fmev depleted cellular levels of the prenylated protein Ras in the sensitive cell line U-937, there was no depletion of cellular Ras levels in the resistant cell line EL-4, but rather, there was a shift of Ras from membrane to cytosol, as expected for inhibition of prenylation. These results suggest that leukemic cells with increased HMG CoA reductase activity produce increased levels of an endogenous mevalonate-derived inhibitor that leads to Ras depletion and suppression of cell growth. As a result, inhibition of the growth of these transformed cells might be specifically accomplished by Fmev.
 ...
PMID:Regulation of proliferation and Ras localization in transformed cells by products of mevalonate metabolism. 927 19

The telomerase activity of various hematologic disorders, including malignant and non-malignant ones is discussed in this paper. In total of 137 cases, each positivity of telomerase activity was MDS = 17/51, overt leukemia from MDS = 6/15, AML = 17/21, ALL = 4/6, CML-CP (chronic phase) = 0/10, CML-BC (blastic crisis) = 4/4, MPD (myeloproliferative disease)-BC = 3/3, CLL = 1/10, MM (multiple myeloma) = 0/6, aplastic anemia = 3/5, essential thrombocytosis = 0/3, and polycythemia vera = 1/3. The MPD-BC showed very high level of telomerase activity as well as CML-BC cases. From the analysis for 18 cases of AML and/or malignant lymphoma patients, significant results showed that the expression of cyclin D/E was not related to telomerase activity in these hematologic disease, as was not the case with breast cancer which was reported formerly.
 ...
PMID:[Analysis for telomerase activity in various hematologic disorders]. 961 44

Thrombopoietin (TPO) is a primary regulator of megakaryopoiesis and thrombopoiesis, and has recently been identified as the ligand for the cytokine receptor MPL. Several lines of evidence suggest that dysregulation of MPL expression or TPO production are implicated in the pathogenesis of various myeloproliferative disorders. For example, mutations in the MPL gene can cause factor-independent growth and a transformed phenotype in vivo, and MPD may be associated with altered expression of the MPL receptor or TPO. Blast cells from patients with acute myelogenous leukemia (AML) often display MPL, and TPO induces some of these to proliferate. In sum, MPL may play a role as part of an autocrine pathway of MPD. While much remains to be clarified about the therapeutic use of TPO in AML, early results suggest it may be useful for platelet donation and/or priming to alleviate chemotherapy-induced thrombocytopenia in other malignant conditions.
Leukemia 1998 Sep
PMID:The role of the MPL receptor in myeloproliferative disorders. 977 96

Twenty patients with poor prognosis AML and four patients in the blastic phase of a myeloproliferative disorder were treated with two 'pulses' of therapy each consisting of two doses of high dose araC (separated by 12 h) followed by a single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was then administered tiw. The median age of the population was 68 years with 88% of patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia of 58% of patients either entered a CR or reverted to preleukemic state. For patients under 70 years of age, treatment produced 62% CRs with a leukemia free decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36% of patients having a leukemia free decision marrow.
 ...
PMID:Poor prognosis acute myelogenous leukemia: 1 - response to treatment with high dose cytarabine/mitoxantrone/ethyol @ (Amifostine). 1093 21


1 2 3 Next >>