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)

Pulmonary distress symptoms and thrombotic complications are side-effects of all-trans-retinoic acid (ATRA) therapy for remission induction in acute promyelocytic leukaemia (APL). The ATRA-induced increase of leukaemic cell adhesive molecules may be responsible. To explore this we used a functional assay to study the effect of ATRA treatment on the adhesion of blast cells to cultured human endothelial cells (EC), endothelial cell matrix (ECM), and interleukin 1beta-activated EC (IL1 + EC). NB4 cells, a maturation-inducible human promyelocytic leukaemia cell line, were treated with 1 microM ATRA or the vehicle (control), labelled with 51Cr and tested in the adhesion assay. ATRA increased NB4 adhesion to EC (P<0.01), ECM (P<0.001) and IL1 + EC (P=n.s.). An inhibition study with anti-EC adhesion receptors MoAbs indicated that anti-E-selectin, anti-VCAM-1 and anti-ICAM-1 effectively inhibited cell adhesion to IL1 + EC (18+/-7%, 45 +/-6.9% and 29+/-6% inhibition, respectively) and to unstimulated EC. Preincubation of ATRA-treated NB4 cells with MoAbs anti-VLA4 and anti-LFA1, the VCAM-1 and ICAM-1 counter-receptors respectively, resulted in a significant inhibition of adhesion. Cytofluorimetric analysis of the NB4 cell membrane molecules confirmed the increase under ATRA of VLA4, LFA1, MAC1 and ICAM-1. Therefore ATRA increases NB4 cell adhesion to the endothelium and the subendothelial matrix. These findings parallel the increment of NB4 surface adhesive molecules, among which VLA4 and LFA1 appear to play an important part. These mechanisms may contribute to the complications of ATRA therapy in APL.
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PMID:All-trans-retinoic acid increases adhesion to endothelium of the human promyelocytic leukaemia cell line NB4. 863 29

Abnormal adhesive interaction between bone marrow stroma and progenitors, one of the causes of unregulated proliferation in chronic myelocytic leukaemia (CML), may be caused by some alterations in adhesion molecules on CML progenitors. We investigated the expression of adhesion molecules (CD44, VLA-5, VLA-4, LFA-1, ICAM-1, L-selectin and c-kit) on bone marrow CD34++ cells from 16 CML patients by three-colour flow cytometry. The mean percentage of cells expressing L-selectin in the CD34++CD38+(or)++ fraction from untreated CML patients was significantly lower, and that in the CD34++CD38- fraction tended to be lower than that from normal controls. Among 11 CML patients treated with interferon-alpha (IFN-alpha), the mean percentage of the cells expressing L-selectin in the CD34++CD38- fraction from three patients with a low percentage of Ph1(+) cells in bone marrow was significantly higher than that from five patients with a high percentage of Ph1(+) cells. In addition, L-selectin expression rate was inversely correlated to the percentage of Ph1(+) cells. There was no significant difference between the untreated patients and normal controls with regard to the expression rates of the other adhesion molecules in each CD34++ fraction except LFA-1. These data suggest that decreased L-selectin expression in CML CD34++ cells reflects one of the features of malignant CML progenitors.
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PMID:Decreased L-selectin expression in CD34-positive cells from patients with chronic myelocytic leukaemia. 863 30

In this study, we examined expressions of several adhesion molecules (AdMs), i.e. leukocyte function antigen-1 (LFA-1: CD11a/CD18), Hermes homing receptor (CD44) and intercellular adhesion molecule-1 (ICAM-1: CD54), on leukemia cells from 51 adult patients with newly diagnosed acute myeloid leukemias (AMLs) to elucidate clinical significance of these AdM expressions. Those expressions in lymphoid malignancies have been correlated with tumor evolutions, but CD44 was detected in all the AML cases examined and CD54 expression did not associate with their clinical characteristics or outcomes. However, we found that LFA-1 expressions significantly correlated with splenomegaly, resistance to induction chemotherapies and short survival periods in AML patients.
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PMID:Clinical significance of LEA-1 expression in adult acute myeloid leukemia. 864 44

The membrane-bound proteins CD30 ligand (CD30L), CD40L and 4-1BBL are members of the tumor necrosis factor (TNF) superfamily. They are expressed mainly by activated T cells. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, regarded as the malignant components of Hodgkin's disease (HD), display high levels of the counter-receptors for these ligands, ie CD30, CD40 and 4-1BB. CD30L and CD40L are known to share some biological activities that can be linked to the unbalanced secretion of cytokines seen in HD. In addition, cell contact-dependent molecules such as adhesion or activation antigens are critically involved in T cell/H-RS cell interactions. Primary and cultured H-RS cells frequently overexpress intercellular adhesion molecule-1 (ICAM-1/CD54), BB-1 (B7-1/CD80) and B70/B7-2 (CD86). Here we show that CD30L and CD40L, but not 4-1BBL upregulate CD54 expression by cultured H-RS cells on the mRNA and protein level, as a result of transcriptional gene activation. Furthermore, enhanced CD54 surface expression by these cells is accompanied by increased shedding of surface-bound CD54, as evidenced by high levels of the 82 kDa soluble (s) CD54 form detectable in culture supernatants after specific stimulation. Addition of CD30L in combination with CD40L to cultured H-RS cells additively enhanced CD54 surface expression and its shedding. These results may give a plausible explanation why sCD54 serum levels are increased in patients with HD.
Leukemia 1996 May
PMID:The CD30 ligand and CD40 ligand regulate CD54 surface expression and release of its soluble form by cultured Hodgkin and Reed-Sternberg cells. 865 79

In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.
Leukemia 1996 Jul
PMID:Expression of costimulatory molecules in human leukemias. 868 98

HL-60 myeloid leukaemia cells are ineffective as stimulators of allogeneic lymphocytes in mixed leucocyte culture (MLC). These cells can be induced to differentiate along the monocytic or granulocytic pathways with or without acquisition of major histocompatibility complex (MHC) class II antigen by various agents. Surprisingly, treatment of HL-60 cells with 10 nM all-trans retinoic acid (RA) for 7 days (HL-60-R7) resulted in a marked increase in MLC stimulation although the cells lacked detectable MHC class II antigen expression at the initiation of the MLC. In contrast, treatment with interferon-gamma (IFN-gamma), with or without RA, induced MHC class II antigen expression but failed to enhance MLC stimulation. Lymphocytes responding to HL-60-R7 were predominantly CD8+ and/or CD16+ and displayed enhanced cytolytic capacity for HL-60 and HL-60-R7 cells as well as natural killer (NK)-sensitive K562 cells. Nevertheless, monoclonal antibodies (mAb) to MHC class II antigens substantially inhibited the MLC and some CD4+ lymphocytes in the responding population were required, although this requirement could be replaced by the addition of interleukin-2 (IL-2). HL-60-R7 (and HL-60) cells were shown to acquire detectable MHC class II antigen expression during the first 3 days of the MLC. Thus a low level of activation by MHC class II+ stimulator cells appears to be required for the response. Analysis of the role of cytokines with costimulatory activity for T cells and/or NK cells indicated that tumour necrosis factor-alpha (TNF-alpha) was important in the proliferative response, while interleukins-1, -6 and -12 and stem cell factor did not seem to be involved. Cell interaction molecules lymphocyte function-associated antigen-1 (LFA-1) (CD11a), intracellular adhesion molecule-1 (ICAM-1) (CD54), ICAM-3 (CD50) and B7.2 (CD86) were up-regulated on HL-60-R7. Blocking mAb to LFA-1 and B7.2 potently inhibited the proliferative response indicating a key role for these molecules in the enhanced immunostimulation by HL-60-R7 cells. The results may have implications for the mechanism of the therapeutic effect of RA in acute promyelocytic leukaemia and may also provide valuable information in regard to the immunogenicity of tumour cells in general.
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PMID:HL-60 myeloid leukaemia cells acquire immunostimulatory capability upon treatment with retinoic acid: analysis of the responding population and mechanism of cytotoxic lymphocyte activation. 877 61

In an in vitro model of monocyte adhesion to glomerular cells, U-937 myelomonocytic leukemia cells irreversibly bind to human mesangial cell monolayers. Adhesion is enhanced in mesangial cells proliferating in response to fetal bovine serum, and in the presence of several cytokines and vasoactive agents. In the present study, co-culture with U-937 followed by removal of non-adherent cells time-dependently decreased viability of mesangial cells, measured either by fluorometry after dual labeling with calcein acetoxymethylester and ethidium homodimer, or by the release of lactate dehydrogenase. The cytotoxic effects of co-culture with U-937 cells were significantly reduced by a combination of free radical scavengers, indicating involvement of reactive oxygen species. U-937 cells also stimulated subsequent proliferation of mesangial cells, assessed by [3H]-TdR incorporation and direct cell counts 24 hours later (from 1,034 +/- 83 to 14,611 +/- 959 and from 2,931 +/- 201 to 19,400 +/- 2,124 cpm/well, quiescent/cycling mesangial cells, respectively, P < 0.01). Controls to rule out TdR incorporation by adherent U-937 cells included selective [3H]-TdR labeling and demecolcine pretreatment. Cell counts at 24 hours confirmed U-937-induced proliferation of quiescent HMC, from 50,575 +/- 3,596 to 143,012 +/- 10,039 cells/cm2 (P < 0.01). Agents that promote U-937 cell adhesion, such as the TxA2 mimetic, U-46619, or angiotensin II, enhanced cytotoxicity while inhibiting the proliferation of both quiescent and cycling mesangial cells, when added during co-culture and the subsequent 24 hours (+1 microM U-46619, 1,875 +/- 131 and 2,546 +/- 125 cpm/well, respectively, 79,793 +/- 5,744 cells/cm2, P < 0.01 vs. U-937 only; +1 microM Ang II, 5066 +/- 560 and 5,784 +/- 306 cpm/well, respectively, 81,068 +/- 4,671 cells/cm2, P < 0.05). Blocking antibodies against the adhesion molecule ICAM-1 and leukocyte counterreceptors (LFA-1, VLA-4) prevented the proliferative response, which could not be duplicated with the conditioned media of U-937 alone or co-cultured with mesangial cells. These findings may reflect the interactions occurring in vivo between infiltrating leukocytes and resident cells during glomerular inflammation.
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PMID:Adhesion of U-937 monocytes induces cytotoxic damage and subsequent proliferation of cultured human mesangial cells. 884 Feb 68

To investigate whether the lymphocyte homing receptors, adhesion molecules regulating normal lymphocyte traffic, influence the dissemination of lymphoma cells, 24 lymphoma/leukemia cell lines were inoculated into SCID mice subcutaneously, and the correlation between the expression of the adhesion molecules and the metastatic potential of the cell lines was examined. Among the six adhesion molecules examined (LFA-1, ICAM-1, CLA, VLA-4, L-selectin and CD44), L-selectin increased the incidence of lymph node metastasis, and CD44 expression was related to both lymph node and organ (hematogenous) metastasis. A monoclonal antibody to the standard form of CD44 (CD44s), Hermes-3, inhibited the local growth and remote metastasis of CD44+ cell lines. Thus, it is concluded that at least CD44s expression is important in both lymphatic and hematogenous metastasis.
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PMID:Metastatic potential of lymphoma/leukemia cell lines in SCID mice is closely related to expression of CD44. 895 66

Hepatoblastoma is an embryonal tumour of the liver, which often contains tissue components with multidirectional differentiation. The occurrence of cell surface antigens in this tumour has not been studied systematically, and we therefore investigated 20 hepatoblastomas for the expression of common acute lymphoblastic leukaemia antigen (CALLA) and cell adhesion molecules (CAMs) in their different tissue components. Epithelial tumour cells of fetal differentiation contained E-cadherin. This protein did not occur in tumour areas with embryonal or mesenchymal differentiation. In contrast, immature embryonal and anaplastic cells expressed CALLA and the hyaluronate receptor (HCAM, CD44). Both fetal and embryonal areas stained irregularly positive for ICAM-1, which, in contrast, was not present on anaplastic cells. Immature fibrous tissue did not contain any of these molecules except for ICAM-1. However, some cells adjacent to, or enclosed in, osteoid were positive for HCAM and NCAM. Like small undifferentiated hepatoblastoma cells, primitive mesenchymal spindle-shaped cells also expressed CALLA, HCAM, and the polysialylated embryonic form of NCAM strongly. This last is not present on other epithelial or mesenchymal tumour cells. Hepatoblastoma cells of varying differentiation express distinct patterns of CAMs and CALLA. Our results give further insight into their histogenesis and cellular interactions and may explain their variable ability for invasive growth and formation of metastases.
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PMID:Expression of cell adhesion molecules and common acute lymphoblastic leukaemia antigen in hepatoblastoma. 897 59

All trans-retinoic acid (ATRA) induces complete remission in acute-promyelocytic-leukemia (APL) patients. This study investigated the adhesive properties of APL cells for the endothelium and the extracellular matrix, their motility and the effect of ATRA on these functions. Blasts from 7 APL patients adhered to resting and IL-1-activated endothelium, to the same degree as normal PMN. Adhesion was partially mediated by ICAM-1 and, for IL-1-activated endothelium, by VCAM-1 and E-selectin. These cells showed less adhesiveness for the matrix than PMN, although they maintained the same substrate preference: they adhered to fibronectin and thrombospondin, but not to laminin and type-IV collagen. Exposure to ATRA in vitro (1 microM for 48 to 96 hr) increased the adhesiveness of APL cells; this effect was particularly evident in the case of sub-endothelial matrix and fibronectin. A similar increment in adhesiveness was observed when comparing cells from 2 patients before and after treatment with ATRA. APL cells migrated in response to fMLP and motility was increased by ATRA. In conclusion, APL cells were less adhesive to the matrix than PMN, but treatment with ATRA considerably enhanced their adhesive properties. This could be important in determining the efflux of leukemic cells from the bone marrow and their tissue infiltration during ATRA therapy.
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PMID:Effect of all trans-retinoic acid (ATRA) on the adhesive and motility properties of acute promyelocytic leukemia cells. 898 93


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