UMLS:C0023473 - FACTA Search

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Query: UMLS:C0023473 (chronic myeloid leukemia)
18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dipyridamole strongly inhibited spontaneous in vitro proliferation of peripheral blood mononuclear cells from patients with acute myelogenous leukaemia (n = 9), chronic myelogenous leukaemia in first chronic phase (n = 4) and blast phase (n = 1). Theophyllamine and verapamil also inhibited proliferation of leukaemia cells from all patients except the CML patient in blast phase where only minimal inhibition was seen. Only dipyridamole caused strong inhibition in concentrations corresponding to the therapeutic serum level, and this inhibition was not influenced by the presence of high levels of interleukin 2.
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PMID:Effect of dipyridamole, theophyllamine and verapamil on spontaneous in vitro proliferation of myelogenous leukaemia cells. 158 6

Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLAad and SLAdd hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell-mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLAad animal and an immunized SLAdd animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine.
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PMID:The failure of skin grafting to break tolerance to class I-disparate renal allografts in miniature swine despite inducing marked antidonor cellular immunity. 175 67

Studies have shown that recombinant human alpha interferon (rIFN alpha) inhibits the growth of colonies of multipotential stem cells from human bone marrow. This report demonstrates that rIFN alpha inhibits the growth of such colonies from the bone marrow of patients with chronic myelogenous leukemia (CML) to a greater extent than from bone marrow of healthy individuals. It also shows that T lymphocyte colonies subcloned with interleukin 2 (IL-2) from CML mixed colonies were inhibited more by rIFN alpha than were similar colonies subcultured from normal mixed colonies. The report demonstrates that the Ph' chromosome is present in such T cell colonies subcultured from CML mixed colonies. When mixed colonies were grown from CML bone marrow in the presence of rIFN alpha, Ph' negative colonies were observed, whereas no such Ph' negative mixed colonies grew from a similar number of bone marrow cells incubated without rIFN alpha. These observations confirm that T lymphocytes derived from bone marrow stem cells are from the CML clone, and that the inhibition of growth of Ph' positive colonies, by rIFN alpha permits the growth of residual normal stem cells. The disappearance of the Ph-chromosome in subclones of T lymphocytes supports the notion of nonclonal hematopoiesis in patients with CML.
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PMID:Restoration of nonclonal hematopoiesis in chronic myelogenous leukemia with interferon alpha. 235 May 91

Peripheral blood specimens were obtained from 22 patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) (16 in chronic phase, 2 in an accelerated phase, and 4 in blast crisis). Studies were performed to determine the frequency of the presence of the Ph1 chromosome in cells of lymphoid lineages. Rosetted (E+) lymphocytes (T lymphocytes) from nine patients in chronic phase and one patient in blast crisis were stimulated with T cell growth factor interleukin 2 (IL-2) and/or phytohemagglutinin (PHA). All ten patients had sufficient T lymphocyte metaphases for analysis and of a total of 461 metaphases examined, only one contained the Ph1 chromosome. Nucleated cells of density less than 1.077 g/mL were infected with Epstein-Barr virus (EBV). Following infection, cell lines were established from individual colonies attached to egg albumin-coated Lab-Tek slide chambers (clonal cell lines) or from suspension culture in 96-well tissue culture cluster dishes (nonclonal cell lines). Cell surface and intracellular marker analysis confirmed the B lymphocyte phenotype of all the cell lines examined. B lymphoblastoid cell lines were established from 16 of the 22 patients. All lines from 12 patients were Ph1-negative. From two chronic phase patients, both Ph1-positive and Ph1-negative lines were established. From one patient in an accelerated phase, only Ph1-positive lines were established. From another patient in blast crisis (of myeloblastic phenotype), only Ph1-positive lines were established initially; however, five months later, after the patient had been treated with mitoxantrone, only Ph1-negative lines were derived from this patient. Based on these results, it appears that most B cells and mature T cells in most CML patients are Ph1-negative, but that about 25% of patients have predominantly Ph1-positive B cells or a mixture of Ph1-positive and Ph1-negative B cells that are capable of growing as established cell lines after transformation with EBV.
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PMID:Incidence of involvement of the B and T lymphocyte lineages in chronic myelogenous leukemia. 299 59

Expression of interleukin 2 (IL-2) receptor (Tac antigen) on leukemic cells from 4 patients with acute lymphocytic leukemia (ALL) and 3 patients with blastic crisis of chronic myelogenous leukemia (CML-BC) was examined. Cells from 6 out of 7 patients did not carry immunoglobulins on their surfaces, but reacted with monoclonal antibodies (mAb) detecting B-cell related antigens such as B1, OKB2 and Leu12. Cells from two cases expressed Tac antigen immediately after cell separation. Phorbol 12-myristate 13-acetate (PMA) could induce Tac antigen in all cases. SDS-PAGE analysis of immunoprecipitates by anti-Tac mAb demonstrated that the molecular weight of Tac antigen on most of the leukemic cells was similar to that of Tac antigen present on Con A-stimulated normal lymphocytes. These leukemic cells poorly responded to exogenous recombinant IL-2. These findings suggest that IL-2 may interact with the immature and mature B cells, and play an important role in the differentiation of B lymphocytes.
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PMID:Expression of Tac antigen on human immature B-cell lineage leukemic cells. 308 29

To evaluate the membrane marker profile of human basophils a panel of well-established monoclonal antibodies (MoAbs, n = 60) was used for a combined toluidine/immunofluorescence staining procedure. Myeloid-associated MoAbs (particularly MoAbs against the LFA-1 family (CD11, CDw18), MoAbs directed against lactosylceramide (CDw17), anti-glycoprotein (gp) 150 MoAbs MCS 2 and MY 7 (CDw13), anti-gp 67 MoAb MY 9, anti Fc gamma-receptor (mol wt 40 kd) MoAb CIKM5, anti-CR 1 MoAb E 11, and the antiglycolipid MoAb VIM-2) were reactive with basophils, indicating a close relationship to other mature myeloid cells. Under normal conditions, basophils surprisingly express at least three activation-linked structures not detectable on mature neutrophils, ie, the p45 structure defined by MoAbs OKT-10 and VIP-2b, the p24 structure identified by the CD9 MoAb BA-2, and the receptor for interleukin 2 (IL 2) recognized by three different MoAbs (anti-TAC, IL2RI, anti-IL 2). Moreover, under short-term culture conditions basophils both in mononuclear cell (MNC) suspension and as purified fractions display the HLA-DR and T4 antigens. The neutrophilic/eosinophilic structure 3-fucosyl-N-acetyllactosamine is expressed on basophils only after neuraminidase treatment. Basophils were not stained at all by CD 16 MoAbs directed against the Fc gamma-receptor (mol wt 50 to 70 kd) of neutrophils, by the MoAb 63D3 (CDw12) recognizing the monocyte/granulocyte-associated p 200 antigen, and by the CDw 14 antibodies (VIM-13, Mo 2) defining the monocyte-specific structure p 55. Enriched basophils freshly obtained from chronic granulocytic leukemia (CGL) patients yielded identical results in FACS analyses. In summary, these data indicate that basophils generate a unique combination of surface determinants and possibly represent an activated cell population.
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PMID:Human blood basophils display a unique phenotype including activation linked membrane structures. 311 89

The influence of exogenous interleukin 2 (IL-2) on the immunosuppressive effect of cyclosporine in the mixed lymphocyte response (MLR) was examined. Results show that addition of exogenous IL-2 to a MLR containing graded doses of CsA (0.01-2.5 micrograms/ml) restored a normal proliferative response to alloantigens. In contrast, the effect of exogenous IL-2 on the induction of cytotoxic lymphocytes in primary MLR in the presence of CsA was variable. At the highest doses of CsA (0.5-2.5 micrograms/ml), no cytotoxic T cell activity could be detected, regardless of the presence of exogenous IL-2. However, at a lower dose of CsA (0.1 microgram/ml) that routinely resulted in the total inhibition of cytotoxic T cell induction, addition of exogenous IL-2 resulted in significant levels of detectable cytotoxic T cell activity. The effect of time-sequential addition of CsA or CsA-plus-exogenous-IL-2 on the proliferative and CML responses in MLR was also examined. Results show that addition of CsA to ongoing primary MLR cultures within the first 48-96 hr of culture results in the significant inhibition of the proliferative and CML response in MLR. Addition of CsA-plus-exogenous-IL-2 to ongoing cultures resulted in no significant inhibition of the proliferative response. In contrast, addition of CsA-plus-exogenous-IL-2 within the first 4 hr of culture did not overcome the immunosuppressive effect of CsA. At 18 hr of culture addition of CsA resulted in complete suppression of the CML response, whereas the addition of CsA-plus-IL-2 resulted in significant levels of cytotoxicity. Thereafter addition of CsA-plus-IL-2 resulted in enhanced levels of cytotoxic T cell activity compared with cultures receiving CsA alone. Taken together, our results suggest that: (1) exogenous IL-2 can overcome the immunosuppressive effect of CsA on the proliferative response in MLR to alloantigens; (2) at high levels of CsA, IL-2 cannot overcome the immunosuppressive effect of CsA on the induction of cytotoxic T-lymphocytes; (3) there are doses of CsA at least in vitro, that allow for the activation of the cytotoxic T cell, presumably with the acquisition of a receptor for IL-2 but without the clonal amplification due to inhibition of IL-2 production; and (4) time-sequential studies revealed that the development of responsiveness to IL-2 by the precursor cytotoxic T cell occurs 4-18 hr after exposure to the stimulating alloantigen with clonal expansion if IL-2 is present.
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PMID:Effect of interleukin 2 on the immunosuppressive action of cyclosporine. 315 79

Defective natural killer (NK) cell populations from patients with chronic myelogenous leukemia (CML), that reacted with both HNK-1+ and B73.1+ antibodies, were obtained by a fluorescence-activated cell sorter (FACS). These fractions, along with NK fractions from normal donors which reacted with both antibodies, were expanded as bulk cultures or clones by limiting dilution, for 4 weeks in the presence of 10% interleukin 2 (IL 2), human type AB plasma, and irradiated human allogeneic mononuclear cells. Successfully established clones from patients with CML, with lytic activity against autologous and more differentiated neoplastic granulocytes, were generated more efficiently from B73.1+ than from HNK-1+ subsets. However, there were no significant differences among the generations of B73.1+ and HNK-1+ clones for both patients and normal donors with lytic activity against NK susceptible K-562 targets. Fresh myeloblast preparations from a blast crisis were found to be more susceptible to lysis by IL 2-proliferative B73.1+ and HNK-1+ clones than were fresh myelocyte preparations from a chronic phase CML patient, which were lytically susceptible to only B73.1+ clones. B73.1+ and HNK-1+ subsets from CML patients demonstrated major histocompatibility complex nonrestricted killing, and showed the following predominant phenotypes: B73.1+T3+T8+ or B73.1+T3+T8- from B73.1+ subsets; and HNK-1-T3+T8+ (initially HNK-1+) from HNK-1+ subsets. In contrast, B73.1+ and HNK-1+ clones from normal donors showed the following predominant phenotypes: B73.1+T3-T8-; and HNK-1-T3-T8- or HNK-1-T3-T8+ (initially all HNK-1+). Short-term in vitro IL 2 or interferon treatment of fresh NK defective subsets from CML patients resulted in minimal cytotoxic augmentation. In contrast, defective NK cells from CML patients, whether HNK-1+ or B73.1+ subsets, proliferated with complete regeneration of cytolytic activity after a 3-4 week exposure to IL 2, but differed in phenotypic profiles as compared to those of normal donors. These observations imply that not only fresh defective NK cells but also the cytotoxically restored clones from CML patients are derived from different NK subsets and may represent undifferentiated forms of NK cells that may be arrested at an early stage of development by yet unknown mechanism(s). In vitro substantiation of autologous leukemia cell killing by IL 2-proliferative NK cell clones is encouraging and may allow for new in vivo immunotherapeutic modalities in CML patients.
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PMID:Natural killer (NK) cell immunodeficiency in patients with chronic myelogenous leukemia. II. Successful cloning and amplification of natural killer cells. 349 52

Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non-Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.
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PMID:T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia. 387 56

The requirements for allogeneic T-cell activation have been studied in experiments with T and/or B cells as stimulator. Although target determinants (TDs, defined by CTL effectors in CML) are present on B and T cells used as target cells, this study indicates that TDs are functionally different when expressed on B and T cells used as stimulator cells, as only B cells can activate CTL precursors. Further, the study confirms that inducing TDs and strong lymphocyte-activating determinants (LADs, defined by proliferation in MLC) can be distinct structures found on two different stimulator B cells. The study suggests that binding of cytotoxic precursor T cells to TDs per se does not allow any detectable activation or start of proliferation and differentiation but requires another function of the stimulator cells in the non-T-cell compartment. The nature of this function is unknown, but it is the background for the first signal received by the TD-specific clones of CTL precursors, resulting in the expression of growth receptors for T-cell growth factor or interleukin 2 which is the second signal necessary for clonal expansion and differentiation.
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PMID:Activation of human alloreactive cytotoxic precursor T lymphocytes. 618 Oct 39

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