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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of recent studies has shown that animals immunized with cytokine secreting primary tumors show resistance against an unmodified tumor cell challenge. In the present study we have evaluated the potential role of IL6, a myeloid differentiation inducing factor, in modifying myeloid leukemia cells, a tumor so far not challenged by this approach. M1 cells transduced with N2 based retrovirus carrying the murine IL6 gene exhibit morphological and functional alterations. Genetically modified M1 cells show significant reduction in the growth constant coefficient and in the ability to form hematopoietic colonies. Flow cytometry analysis demonstrate increased expression of CD11b, CD18, F4/80, FcR and MHC class II, suggesting driven differentiation towards commitment. Transduced cells secrete high level of autocrine IL6 and, upon activation with LPS, high levels of TNF further indicating a functional alteration and differentiation. The insertion of IL6 gene coding for signals of cell activation and improved expression of MHC antigens into myeloid leukemia cells may enable more effective tumor recognition in vivo, and boost the local as well as the systemic immune-mediated anti-leukemia response.
Leukemia 1995 Oct
PMID:Modification of M1 cells by exogenous introduction of IL6 gene: a model for gene therapy of acute and chronic myeloid leukemia in mice. 747 25

Of 235 consecutive patients with de novo acute myeloid leukemia (AML), clonal chromosomal abnormalities were detected in 151 (64%) of them. Twenty-four of the 71 patients with M2 AML had t(8;21), 35 of the 36 M3 patients had t(15;17), and 11 of the 45 M4 leukemia disclosed inv(16). Six of the eight patients with 11q23 abnormality had M4 or M5 subtype of leukemia. The incidence of t(15;17) and t(8;21) was higher in our patients than in patients from most Western countries. Immunophenotyping was performed on 197 patients. Patients with t(15;17) were associated with negativity to HLA-DR, CD11b, and CD34. Patients with t(8;21) expressed CD13 and CD33 less frequently than other patients, but all showed CD15 positivity. Coexpression of lymphoid-associated antigens on the leukemic blasts was detected in 52 patients (26%), including all 7 patients with t(9;22), 3 of the 8 patients with t/del(11)(q23), 2 of the 25 patients with t(15;17), and 2 of the 22 patients with t(8;21). Seven (35%) of the 20 patients coexpressing lymphoid markers showed immunoglobulin heavy chain or T-cell receptor beta-chain gene rearrangements, while only 2 (4%) of the 53 patients without lymphoid antigen expression did so. Patients with inv(16), t(8;21), and t(15;17) had a better prognosis than other patients. Of all surface antigens tested, only CD15, CD11b, and HLA-DR were of prognostic value: CD15 with a higher complete remission (CR) rate and CD11b or HLA-DR with a shorter CR duration. N-ras mutations were detected in 7 (18%) of the 40 patients in the study, including two of the three patients with inv(16). This study demonstrated differences in clinical features, immunophenotypes, and genotypes among different cytogenetic subgroups.
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PMID:Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan. 749 45

The mechanisms of extramedullary leukemic infiltration are not well characterized. The cell-surface glycoprotein CD56, which is identical to the neural cell adhesion molecule, may be involved. Using the Leu-19 antibody and flow cytometric methods, the leukemic blasts of 22% (70 of 314) of patients were CD56 positive. This was most common in acute monocytic leukemia (15 of 18, 83%) and in patients with the cytogenetic abnormalities t(8;21) (seven of 13, 54%) and trisomy 8 (nine of 22, 41%). CD56 expression was not associated with extramedullary leukemic infiltration, but was correlated with positivity for CD11b (p < 0.001), CD14 (p < 0.001) and CD19 (p = 0.018). Although associated with morphologic and cytogenetic features, CD56 expression alone cannot account for most instances of tissue infiltration in acute myeloid leukemia (AML).
Leukemia 1994 May
PMID:Investigation of karyotypic, morphologic and clinical features in patients with acute myeloid leukemia blast cells expressing the neural cell adhesion molecule (CD56). 751 47

The action of two structurally related DNA intercalating agents has been studied and compared, namely 4'-(9-acridinylamino) methanesulphon-m-anisidide (amsacrine, mAMSA) and 1,4-bis(butylamino)benzo[g]phthalazine (ABP) on the cell cycle and differentiation of U-937 human promonocytic leukemia cells. mAMSA (0.1 microM) and ABP (4 microM) reduced the proliferation activity to a similar extent and caused little cell mortality. At these subcytotoxic concentrations mAMSA induced the cells to accumulate at the G2 phase of the cycle, while cycle inhibition provoked by ABP was not phase specific. In addition, mAMSA caused an increase in the cell mass while ABP provoked cell shrinkage. This was consistent with the fact that ABP considerably inhibited protein synthesis, while mAMSA did not significantly affect this activity. SDS/K+DNA precipitation assays indicated that mAMSA, but not ABP, stimulated protein-DNA covalent complex formation. Finally, it was found that mAMSA, but not ABP, elicited the expression of differentiation markers, namely nitroblue tetrazolium reduction, activation of vimentin and leukocyte integrin (CD11b/CD18 and CD11c/CD18) expression, and downregulation of c-myc expression. The DNA intercalators doxorubicin and mitoxantrone, which like mAMSA induced the cells to accumulate at the G2 phase and increased the cell mass, induced the expression of differentiation markers. In contrast, the intercalators aclarubicin and caffeine and the non-intercalator novobiocin, which produced minor alterations on cell-cycle distribution and caused cell shrinkage, did not significantly elicit differentiation. These results support the conclusion that differentiation of myeloid leukemia cells by cytostatic drugs depends on the perturbations of the cell cycle, leading to disproportionate increases in cell mass.
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PMID:The action of the DNA intercalating agents 4'-(9-acridinylamino) methanesulphon-m-anisidide and 1,4-bis(butylamino) benzo[g]phthalazine in U-937 human promonocytic cells: relationship between cell cycle and differentiation. 751 13

We examined the effect of dibutyryl cAMP (dbcAMP) on the expression of LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and VLA-4 (CD49/CD29) and on eosinophilic differentiation of a human leukemia cell line, EoL-1. Dibutyryl cAMP induced eosinophilic differentiation of EoL-1 cells from 6-9 days after the start of culture with down-regulation of CD11a, CD18, and CD49 expression and up-regulation of CD11b expression. Changes in integrin expression, except for CD18, were seen predominantly in the fraction containing eosinophilic granule-positive cells, suggesting that the changes were dependent on eosinophilic differentiation. On the other hand, dbcAMP-induced changes of integrin expression were reversible and were not seen on day 9 when dbcAMP was removed on day 3, whereas eosinophilic differentiation was still present. A combination of G-CSF and TNF-alpha, which also induced eosinophilic differentiation of EoL-1 cells, increased CD11b expression slightly but had no significant effect on the expression of the other integrins. Butyrate and PMA up-regulated CD11b expression without eosinophilic differentiation. The results collectively suggest that the regulation of integrin expression on EoL-1 cells is partly dependent and partly not dependent on eosinophilic differentiation. The possible involvement of protein kinase A and protein kinase C in these changes is suggested.
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PMID:Effects of cyclic AMP on expression of LFA-1, Mac-1, and VLA-4 and eosinophilic differentiation of a human leukemia cell line, EoL-1. 752 82

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor can induce the differentiation of mouse myeloid leukemia M1 cells and also stimulate proliferation of the interleukin-3 (IL-3)-dependent cell line, DA-1a. To determine whether D-factor can induce the differentiation of leukemia cells other than M1 cells, WEHI-3B D+ mouse myelomonocytic leukemia cells were transfected with a plasmid containing mouse D-factor receptor cDNA. Expression of D-factor receptor in transfected cells was determined by binding of [125]D-factor and analyzed by Scatchard's method. The transfected cells had high-affinity D-factor receptors with a dissociation constant of 100 to 200 pmol/L and binding sites per cell varied from 67 to 1,500 among several clones. The cells expressing a high level of D-factor receptor were induced to differentiate by D-factor; about 60% of the cells exhibited the ability to reduce nitroblue tetrazolium and expression of the differentiation antigen Mac-1 (CD11b) on the cell surface increased. The effect of cytokines, which induce the differentiation of M1 cells, on the transfected WEHI-3B cells was examined. The sensitivity to oncostatin M was identical to that against D-factor in the cells of each clone. Expression of D-factor receptor in WEHI-3B cells promoted sensitivity to IL-6 and granulocyte colony-stimulating factor (G-CSF). Induction of differentiation of the cells accompanied the suppression of proliferation. Treatment of the cells with D-factor for longer than 5 days resulted in 50% inhibition of growth. These results indicate that the stimulating effect of D-factor on the differentiation of malignant myeloid cells is not unique to M1 cells.
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PMID:Induction of differentiation of WEHI-3B D+ leukemic cells transfected with differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA. 752 68

Interactions between hematopoietic cells and the stromal microenvironment are mediated by membrane-bound adhesion molecules. As the expression patterns of these molecules may alter the adhesive qualities of leukemic blasts, leukemic samples were investigated for the expression of beta 1-, beta 2-, beta 3-integrins, CD44, the three selectins and several members of the immunoglobulin family. CD44 (167/169), LFA-3 (158/169), the beta 1-integrins VLA-4 (120/123) and VLA-5 (45/51) and the beta 2-integrin LFA-1 (149/157) were found on > 70% of blasts in most cases of leukemias. Other molecules were restricted to specific differentiation stages and lineage. The beta 2-integrins Mac-1 (CD11b/CD18) and gp 150,95 (CD11c/CD18) were preferentially expressed on M4 and M5 subtypes, and NCAM (CD56) was only found on a subset of acute myeloid leukemias (17/113). Unexpectedly, the beta 1-integrins VLA-1 (1/51), VLA-2 (18/123), VLA-3 (5/43), VLA-6 (15/29) and the E-selectin (2/47) were expressed on > 70% blasts on a subset of leukemias of varied phenotype. These molecules were absent on normal CD34+ bone marrow precursors. The simultaneous analysis generally revealed a higher percentage of positive blasts in the blood than in bone marrow. Our observations therefore suggest that in leukemia these antigens are displayed on a non-adherent population that is defective and is unable to convert to an adherent, functionally active conformational state.
Leukemia 1995 May
PMID:Differential expression of adhesion molecules in acute leukemia. 753 15

Peripheral blood cells from a female patient with Ph1-positive chronic myelogenous leukemia (CML) in blast crisis were serially transplanted in BALB/c nude mice for 16 passages. This in vivo cell line, designated CML-N-1, had Ph1 chromosome abnormality and BCR gene rearrangement. The cells expressed CD11b, CD13, CD33, CD34, CD38, and HLA-DR antigens until the 11th passage and subcutaneous tumors produced by these passages were composed of admixtures of immature and maturing cells that differentiated to basophils when cultured in vitro. From the 12th passage on, the tumors became composed mainly of immature cells expressing CD13, CD34, and HLA-DR, and no longer differentiated to basophils even upon in vitro culture. In contrast to the vigorous proliferation in vivo, CML-N-1 cells from any passage failed to proliferate in vitro under standard liquid culture conditions with or without growth factors, such as granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, monocyte colony-stimulating factor, interleukin 3, interleukin 6 and stem cell factor. However, a continuously growing cell line, designated CML-C-1, was established by culturing CML-N-1 cells on feeder layers of mouse bone marrow stromal cells. This mouse bone marrow stromal cell-dependent cell line showed immature cell morphology and expressed early myeloid phenotype positive for CD13, CD34, and HLA-DR. These results indicate that mouse bone marrow stromal cells provide a certain growth factor(s) active on human leukemia cells.
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PMID:Direct transplantation of chronic myelogenous leukemia cells into nude mice and establishment of a leukemic stem cell (Ph1+, CD34+) line dependent on mouse bone marrow stromal cells in vitro. 754 Jun 8

Peripheral blood lymphocytes of 46 recipients of lymphocyte-depleted bone marrow allografts were phenotypically analysed over a period of 1 year. We investigated the repopulation of lymphocyte subpopulations and their relation with clinical parameters such as graft-versus-host disease (GVHD), graft-versus-leukaemia and cytomegalovirus (CMV) infection. The number of repopulated T cells varied strongly between the blood samples of the recipients. In 45% of the recipients the number of T cells recovered to or above normal levels within 3 months after bone marrow transplantation (BMT), whereas the other recipients remained below normal up to 1 year after BMT. In recipients with a high repopulation, the CD8+ T-cell subset contributed more to this high repopulation than the CD4+ T-cell subset. We showed that the majority of T cells of these recipients expressed the alpha beta T-cell receptor, CD8, CD57 and CD11b. HLA-DR was also highly expressed reflecting the activation stage of T cells in these recipients. BMT recipients with a high repopulation of CD8+ T cells showed a lower incidence of leukaemic relapse than recipients with a low repopulation. The 3-year probability of relapse was 19% versus 64% (P = 0.03), respectively. The relative high number of CD8+ T cells at 3 months after BMT was not associated with the incidence of GVHD. In contrast, occurrence of CMV infection after BMT was significantly higher in these recipients. Our results indicate that CD8+ T cells, predominantly CD57+, of BMT recipients with an expansion of these cells represent an in vivo activated cell population. This CD8+ T-cell population may consist partially of cytotoxic cells with anti-leukaemic activity as suggested by a low relapse rate. The signal for the strong expansion of these CD8+CD57+ T cells after BMT is still unclear, but association with CMV infection suggests that viral antigens are involved.
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PMID:Expansion of CD8+CD57+ T cells after allogeneic BMT is related with a low incidence of relapse and with cytomegalovirus infection. 754 Aug 55

A case of 77-year-old female with multiple myeloma (IgG-k) developed acute myelomonocytic leukemia (AMMoL) following a myelodysplastic stage after chemotherapy with melphalancyclophosphamide combinations for 6 years. The leukemic blast cells expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33 and CD34) and T/B lymphoid antigens (CD2, CD4, CD22 and PCA1). Cytogenetic analysis revealed a chromosome deletion -7. Analysis of immunoglobulin genes showed the heavy chain genes in germ line configuration. These findings indicate that the AMMoL was a therapy-related stem cell leukemia and was a clonal origin genetically different from multiple myeloma irrespective of plasma cell phenotype.
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PMID:Acute myelomonocytic leukemia in a patient with multiple myeloma: evidence for different clonal origin. 754 40


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