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

Among 50 cases of acute nonlymphocytic leukemia (ANLL) with available cytogenetic data seen in our section since May 1988, two were found to carry a monosomy 21 abnormality which has been rarely reported in hematologic malignancies. The first case is a 58-year-old male with a diagnosis of AML, FAB M2, who died of refractory leukemia 9 months later. The other case is a 59-year-old female with AML, FAB M2. Complete remission was achieved initially but she died of sepsis 3 months later with no evidence of leukemic relapse. Monosomy 21 is not yet recognized as a nonrandom cytogenetic abnormality in ANLL, whereas its unusual predilection in AML, especially the FAB M2 or M4 categories, as noted in our study and others' reports, have raised this possibility. Further studies and the accumulation of new cases are needed in the hope of defining it as a subtype of ANLL.
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PMID:Monosomy 21 in two patients with acute nonlymphocytic leukemia. 163 89

Amphotropic murine retrovirus 4070A was demonstrated to be highly leukemogenic when inoculated intravenously into adult DBA/2 mice that were undergoing an intense chronic inflammatory response, but was nonleukemogenic in the absence of inflammation. The virus-induced promoonocytic leukemias, designated AMPH-ML, are similar morphologically and in cell surface marker expression to monocytic leukemias, called MML and MF-ML, previously shown to be induced by Moloney murine leukemia virus and MF-3 virus (a recombinant between Friend murine leukemia virus and Moloney murine leukemia virus) and resemble certain mature acute monocytic leukemias in humans (AML subtype M5). Approximately two-thirds of the AMPH-MLs (subgroup I) were demonstrated to have alterations in the 5' end of the c-myb locus, an event which occurs in 100% of MML and MF-ML. Data indicate that proviral insertions in AMPH-ML subgroup I resulted in aberrant c-myb mRNA expression and truncation of its translation product at the amino terminus. Approximately one-third of the AMPH-MLs (subgroup II) had not undergone any DNA rearrangements at the c-myb locus. In addition, their transcripts and protein products were of normal size. These latter leukemias also had not undergone DNA rearrangements in c-myc, although retroviruses expressing myc have previously been shown to induce monocyte-macrophage tumors in mice undergoing a chronic inflammation. That subgroup II leukemias had at least one clonal viral insertion suggests that there may be other sites in the cellular genome that can be activated by insertional mutagenesis in these murine acute monocytic leukemias.
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PMID:Acute myeloid leukemia induction by amphotropic murine retrovirus (4070A): clonal integrations involve c-myb in some but not all leukemias. 164 85

Two different classes of therapy-related acute myeloid leukemia (t-AML) seem to emerge. One class follows therapy with alkylating agents, increases in frequency with age, often presents with myelodysplasia (MDS), responds poorly to chemotherapy, and shows monosomy 7(-7), monosomy 5(-5), or loss of various parts of the long arms of these chromosomes (5q- and 7q-). The other class is related to therapy with cytostatic drugs targeting at DNA-topoisomerase II, often presents with overt leukemia, responds more favorably to chemotherapy, and shows balanced chromosome aberrations, primarily translocations involving chromosome bands 11q23 and 21q22. These two classes of t-AML may have their counterparts in de-novo acute myeloid leukemia (de-novo AML).
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PMID:Two different classes of therapy-related and de-novo acute myeloid leukemia? 165 39

Anti-SSEA-1 which binds to glycoconjugates with a Gal beta 1-4(fuc alpha 1-3)GlcNAc epitope and VIM-2 which binds to gangliosides with a NeuAc alpha 2-3GlcNAc beta-4(FUC alpha 1-3) GlcNAc beta 1-3Gal-epitope were used to determine the expression of their corresponding carbohydrate antigens in human leukocytes and leukemia cells. Expression of these antigens was evaluated by immunohistochemical staining of plastic embedded sections of bone marrow or isolated cells, and by immunostaining of isolated glycosphingolipids separated by thin layer chromatography. The expression of both antigens was restricted to normal and leukemic myeloid cells. A range of positive immunohistochemical staining was found among normal marrow myeloid precursors, with myeloblasts giving weaker staining than more mature cells (promyelocytes, myelocytes, metamyelocytes). A similar trend was observed with leukemia cell lines, in that the myeloblastic cell line KG1 was weakly stained compared to the partially differentiated cell line HL-60. Immunohistochemical staining of marrows from acute leukemia patients showed that the VIM-2 antigen is more strongly expressed than the SSEA-1 antigen. Interestingly, both antibodies stained AMMoL cells more intensely than AML cells. Granulocytes from marrows of chronic myelogenous leukemia (CML) patients were intensely stained by both antibodies, whereas lymphocytic leukemias (acute lymphocytic, chronic lymphocytic and hairy cell marrows) were negative. Thus, although both antigens are restricted to myeloid cells there are differences in the level of expression depending on the level of cell maturity. Immunostaining of glycosphingolipids isolated from myeloid cells demonstrated that the SSEA-1 epitope is carried by several neutral glycosphingolipids and that the VIM-2 epitope is carried by three or more gangliosides. Major SSEA-1 glycosphingolipids, with seven to more than ten monosaccharides, are expressed by all myeloid cells regardless of the level of maturity, although quantitative differences are apparent in different patient samples. Two strongly immunoreactive VIM-2 gangliosides with ten and twelve monosaccharides, respectively were found in myeloid cells. The ratio of these two gangliosides varied dramatically, with greater amounts of the more complex ganglioside being present in most cell samples. Normal neutrophils and CML cells had much greater quantities of the VIM-2 gangliosides than acute leukemia cells. This observation correlates with our earlier findings that: (1) acute leukemia cells have less total ganglioside than granulocytes and (2) acute leukemia cells have a predominance of short chain gangliosides (i.e. less than five monosaccharide units). Finally, both CML cells and normal neutrophils express a shorter chain VIM-2 ganglioside, which was not detected in acute myelogenous leukemia cells.
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PMID:Distribution of VIM-2 and SSEA-1 glycoconjugate epitopes among human leukocytes and leukemia cells. 169 Mar 17

Within normal hemopoiesis, the intranuclear DNA polymerase TdT seems to be exclusively expressed by T and B lymphoid precursor cells. Double staining experiments showed that TdT can also be expressed in blast cells of certain acute myeloid leukemias. Recent reports described a very strong association between TdT expression and rearrangements of IgH and TcR genes in such AML specimens, suggesting a predominant lymphoid commitment of these TdT positive AML blasts. When submitting 24 serologically and morphologically well-characterized TdT positive AML specimens for additional genotypic analysis to determine the IgH and TcR gene configuration, we observed that only four had clonally rearranged IgH and/or TcR genes, whereas 20 had germ line configuration. This frequency is clearly lower than previously reported and not necessarily different from rearrangement frequencies reported for TdT negative AML (4-40%). It would seem to us, therefore, that the expression of TdT in otherwise well-defined AML blasts is not necessarily associated with a higher frequency of immunoglobulin and/or T cell receptor gene rearrangement.
Leukemia 1990 Apr
PMID:Terminal deoxynucleotidyl transferase and CD7 expression in acute myeloid leukemias are not associated with a high frequency of immunoglobulin and/or T cell receptor gene rearrangement. 169 41

The effect of serum from 32 AML patients on the normal human myeloid differentiation and the hexamethylene-bisacetamide induced granulocytic differentiation of HL-60 promyelocytic leukaemic cell line was studied. Nonadherent normal mononuclear marrow cells were cultured in vitro at a concentration of 5 x 10(5) cells/ml for 6 days with each of the 32 AML sera. Ten normal human AB sera were used as control. The results showed an inhibitory activity on both morphological and functional differentiation of normal human myeloid immature marrow cells by 29 out of the 32 AML sera tested. These 29 AML sera were added to cultures of HL-60 (2.5 x 10(5)/ml) leukaemia cell line which incorporated 2 mM hexamethylene-bisacetamide for 6 days. The results showed no significant inhibition of hexamethylene-bisacetamide induced granulocytic differentiation by any of the 29 AML sera. The efficacy of hexamethylene-bisacetamide in inducing differentiation in the presence of inhibitory factors suggests a possible role in the treatment of AML patients.
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PMID:Effect of AML serum on normal human myeloid differentiation and hexamethylene bisacetamide-induced granulocytic differentiation of the human HL-60 promyelocytic leukaemic cell line. 169 70

The cells from some patients with acute myeloblastic leukemia will secrete autostimulatory cytokines in tissue culture without the addition of stimulators such as phorbol 12-myristate 13-acetate. Production of interleukin-1 beta (IL-1 beta), for example, has been observed in up to 50% of cases. In order to investigate the nature of the cell secreting IL-1 beta in AML, we used an antisense RNA probe to detect specific IL-1 beta transcripts in individual leukemic cells by in situ hybridization. In fresh, uncultured cells, IL-1 beta transcripts were observed in 1-40% of undifferentiated leukemic blast cells in 17 of 19 cases. In situ hybridization was at least as sensitive as Northern blot analysis in detecting IL-1 beta transcripts. No correlation of IL-1 beta transcript expression with FAB classification was observed. Normal blood and bone marrow mononuclear cells did not contain cells expressing IL-1 beta transcripts. These results support the concept that the regulation of cytokine genes in AML cells is aberrant.
Leukemia 1990 Jul
PMID:Demonstration of interleukin-1 beta transcripts in acute myeloblastic leukemic cells by in situ hybridization. 169 3

In order to minimize the interactions of clonogenic cells with accessory cells and characterize the direct effect of recombinant hematopoietic growth factors (HGF) on acute myelogenous leukemia colony-forming cells (AML-CFU), the response of CD34+ AML-CFU to individual or combined recombinant HGF, i.e., interleukin-1 (IL-1), interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF), was studied in 10 patients and compared with the growth response obtained from unfractionated marrow cells. IL-3 and GM-CSF had a similar stimulating activity on AML-CFU growth. G-CSF resulted the most efficient stimulus for colony formation and was additive or synergistic with IL-3 and GM-CSF, M-CSF, used alone, had a negligible stimulating activity. When CD34+ cells were used, IL-1 by itself had a low stimulating activity and displayed little or no synergy with IL-3, GM-CSF, and G-CSF. On the contrary, when unfractionated cells were used, IL-1 was very effective in inducing AML-CFU formation and was markedly synergistic with IL-3 and GM-CSF. These results show that IL-1-induced leukemic colony formation is prevalently mediated by accessory cells. IL-6 supported AML-CFU growth in seven of 10 cases, thus showing a direct effect on CD34+ leukemic cells, and enhanced the growth of IL-3-(+47 to +167%) and GM-CSF-dependent (+60 to +110%) AML-CFU. Recloning studies of single colonies demonstrated that primary CD34+ AML-CFU, stimulated by IL-3 and GM-CSF, generated secondary and tertiary colonies, whereas primary AML-CFU stimulated by G-CSF and IL-6 failed to give rise to secondary colonies, thus indicating a complete suppression of self-renewal. Sequential recloning of colonies grown in the presence of IL-3 + IL-6 demonstrated that addition of IL-6 and IL-3-containing plates resulted in a nearly complete suppression of self-renewal. In conclusion, these results demonstrate the heterogeneity of the CD34+ leukemic cell fraction and indicate the existence of complex regulatory events at the level of CD34+ leukemic cells. Data obtained from recloning experiments are of therapeutic interest in view of the clinical application of HGFs in the treatment of myeloid leukemias.
Leukemia 1990 Aug
PMID:Growth of CD34+ acute myeloblastic leukemia colony-forming cells in response to recombinant hematopoietic growth factors. 169 11

Acute leukemia has become a curable disease. In 3 studies for adult AML (BHAC-DMP, BHAC-DMP (II) and M-85) at Nagoya University Hospitals from 1979 to 1987, intensive induction resulted in higher cure rate, and the reduction of the blasts in bone marrow at 2 weeks after the initiation of therapy to less than 20% was the most important prognostic factor to predict the long CR. However, it seemed impractical to give very intensive chemotherapy during the induction because of high frequency of complications due to prolonged myelosuppression. Thus, consolidation should be as intensive as possible. In M-85 protocol, the predicted 5-years survival and disease-free survival (DFS) of CR cases are 70 and 53% respectively. The result of JALSG-AML 87 study seems to confirm the above result. As for the indication of bone marrow transplantation (BMT) at the first CR for adult AML, only a prospective randomized study will answer this important question. In case that DFS of chemotherapy will exceed 40 to 45%, it seems be wise to give chemotherapy first, and then BMT when the leukemia relapse. Differentiation induction therapy seems to be indicated in acute promyelocytic leukemia, although a confirmative study is awaited.
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PMID:[Recent progress in the treatment of acute leukemia]. 171 2

To assess effects of chemo- and radiotherapy on the endocrine system 31 children with acute leukaemia and NHL (3 AML, 24 ALL, 4 NHL) were investigated. Children were treated according to modified BFM protocols. 25 patients were before, 5 during and one after puberty (2 to 16 y.). Before treatment, during induction therapy, during cranial irradiation, 4-6 weeks later and during maintenance therapy the following hormone values were estimated: TSH and prolactin basal and 30 min. after TRH (5 micrograms/kg i.v.), LH and FSH basal. Final investigations included total T4 and T3. In conclusion, chemo- und radiotherapy lead to transient elevations of TSH and prolactin in a few patients, but without proof for permanent disorders. Due to the fact all 3 patients with hyperprolactinaemia showed high prolactin levels (700 to 770 mU/l) already before treatment it is unlikely therapy was the main cause of these observed alterations. Although basal LH and FSH values were in normal ranges for age the increasing values after cranial irradiation in prepubertal children may reflect a possible initiation of early maturation, reported by others. Furthermore a retrospective growth study was performed in children treated with 2 different protocols. Protocol LSA2L2 used in the past before 1981 resulted in a permanent reduction of the height. In contrast, the mean SDS for height in children treated with protocol VII declined only during the intensive period of treatment. A catch-up growth occured already during maintenance therapy. Prophylactic cranial irradiation with 18 Gy in our patients under protocol LSA2L2 did not affect growth during the first 5 years after diagnosis.
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PMID:Prospective study on the influence of radiochemotherapy on pituitary function in children with acute leukaemia and NHL. 171 81


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