Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Until recently, T cells were believed not to be involved in chronic myeloid leukemia. We describe an example of CML in T lymphoblastic crisis with massive generalized lymphadenopathy in which the blasts were CD2(+), CD5(+), and CD7(+), variably CD1(+) and CD3(+), and both responded to and could be induced to produce the T cell growth factor, interleukin-2. Additionally, the blasts were shown to contain the CML-related tyrosine kinase P210bcr-abl rather than the smaller kinase associated with Ph1(+) ALL. Finally, the participation of the T lymphoid lineage in the CML clone was proven by the presence of the same BCR rearrangement in blasts as in granulocytes, suggesting the existence of a bone marrow progenitor common to the T cell and myeloid lineages.
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PMID:Chronic myeloid leukemia arising in a progenitor common to T cells and myeloid cells. 216 6

The anti-leukemia potential of natural killer (NK) cells has been evaluated in 40 patients transplanted for chronic myelogenous leukemia (CML) to determine whether differences in NK cell function were correlated with subsequent leukemic relapse. Cells from patients and their donors were tested in 51Cr release assays against fully allogeneic CML targets and against cultured K562 targets; cells from 26 patients were tested against host-derived CML targets that were cryopreserved before transplantation. Cultured CML targets (K562) were highly susceptible to lysis by freshly isolated peripheral blood lymphocytes (PBL) and to a greater degree by PBL cultured in medium containing interleukin-2 (IL-2) in all assays performed. In contrast, noncultured CML targets were lysed only by IL-2-activated cells from a subset of patients. When present, lytic activity to CML targets was detectable as early as 3 weeks after bone marrow transplantation, and remained positive throughout the posttransplant period. Optimal lytic activity developed within the first week of culture and required greater than or equal to 250 U/mL of IL-2 in the culture medium. Lytic activity to fully allogeneic and host-derived CML targets appeared to be mediated by CD16+ and CD56+ cells but not by CD3+ cells. Lysis of allogeneic CML targets was variable, but patients could be divided into two groups: those with and those without lytic activity to the majority of targets tested. The basis for the differences in lytic activity could not be ascribed to target susceptibility to lysis, the proportion of NK cells in the cultures, or to the phenotype of the NK cell subsets in the cultures. When tested in parallel, the lytic activity of donor and recipient cultures against host-derived CML targets was highly correlated, suggesting that there may be inherent differences in the ability of NK cells to recognize CML targets. The risk of relapse for patients who failed to generate lytic activity against host-derived CML targets was significantly increased over that for patients with lytic activity against host leukemia. These data indicate that posttransplant immunotherapy with IL-2 designed to activate NK cells will likely augment the graft-versus-leukemia potential of the graft.
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PMID:Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia. 218 8

We studied the in vitro effects of lymphokine-activated killer (LAK) cells from the peripheral blood of chronic myeloid leukemia (CML) patients after allogeneic and syngeneic bone marrow transplantation (BMT). LAK cells were generated by incubating peripheral blood mononuclear cells from patients post-BMT with recombinant interleukin-2 (IL-2) (500 U/mL) in 10% AB serum for 7 days. They were phenotyped and tested for activity in a standard 4-hour 51Cr release assay (n = 37) and in a CFU-GM assay (n = 24). We found that the LAK cells were mainly activated natural killer cells, but some were CD3+ T cells. In the 51Cr release assay LAK cells from 20 of 33 (61%) allogeneic and 2 of 4 syngeneic recipients killed recipient CML cells and in 22 of 37 (60%) cases also killed the HLA disparate CML cells. In the CFU-GM assay the LAK cells incubated together with the CML cells in liquid culture before plating inhibited (P less than .05) colony growth in 16 of 22 allogeneic and 2 of 2 syngeneic recipients. Cell-cell contact was necessary for optimal effect. There was little or no inhibition of proliferation of donor marrow CFU-GM. This in vitro graft-versus-leukemia (GVL) effect could also be demonstrated after LAK effectors were depleted of CD3+ T cells. It was inducible in recipients of both T cell-depleted and T cell-replete donor marrow and in recipients with or without graft-versus-host disease. These results suggest that a major histocompatibility complex-unrestricted GVL effect is inducible following allogeneic and syngeneic BMT. The use of IL-2/LAK cells after BMT could reduce the risk of relapse.
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PMID:Induction of in vitro graft-versus-leukemia activity following bone marrow transplantation for chronic myeloid leukemia. 224 25

Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.
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PMID:Induction of a syngeneic graft-versus-leukemia effect following bone marrow transplantation for chronic myeloid leukemia. 236 84

Lymphokines represent a new group of substances that have engendered increasing interest in the context of cancer therapy. They are products of the lymphoid system that can now be produced in pure form as a consequence of advances in gene cloning technology. alpha-Interferon has been tested in clinical trials for several years, and has been found effective in the treatment of patients with hairy cell leukemia, chronic myelogenous leukemia, Kaposi's sarcoma (AIDS) and renal cell cancer. Interleukin-2 has shown impressive antitumor activity in patients with melanoma or renal cell cancer, particularly in combination with lymphokine-activated killer cells, although at very high doses with correspondingly severe toxicity. The clinical testing of tumor necrosis factor is in an early stage. The introduction of this class of agents has opened new perspectives for cancer therapy.
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PMID:[Interferons, interleukin-2 and tumor necrosis factor. New approaches to cancer therapy]. 243 34

Basophils were isolated and propagated in large numbers from the blood of patients with chronic myelogenous leukemia. Propagation over 4-6 weeks of culture was dependent upon a growth factor(s) other than interleukin-2 obtained from a lectin-stimulated clone of the Jurkat cell line. Evidence that these basophils were dividing during culture included an increase in both the number of basophils and the histamine content of the cultures over time, as well as ultrastructural studies that demonstrated basophil cell division. The cells also had the capacity to be stimulated in an IgE-dependent manner characteristic of basophils. Cultured basophils passively sensitized with IgE underwent noncytotoxic degranulation after stimulation with specific antigen. Antigen-stimulated basophils released histamine, leukotrienes B4 and C4 and other 5-lipoxygenase products of arachidonic acid metabolism. Culture models such as this may permit the propagation and purification of sufficient numbers of basophils to allow biochemical and immunological analyses of basophil physiology.
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PMID:Propagation and characterization of human blood basophils. 245 92

The monocyte, monocyte conditioned media (MoCM), giant cell tumor conditioned media (GCT) and a purified colony-stimulating factor (G-CSF) promote granulocyte-macrophage progenitors (CFU-GM) growth and differentiation along the neutrophil lineage and also induce alkaline phosphatase (NAP) synthesis in the neutrophilic cells of normal subjects and of patients with chronic phase chronic myelogenous leukemia (CML). However, it is not known if granulocyte-macrophage-CSF (GM-CSF), macrophage-CSF (CSF-1) or other cytokines can induce NAP synthesis from the neutrophilic cells of CML patients. The objective of this study were (a) to ascertain which of the three CFU-GM CSFs would induce NAP synthesis, and (b) to test if any of the other cytokines--interleukin-1 (IL-1), interleukin-2 (IL-2), alpha- and gamma-interferons (alpha-INF and r-INF), and phytohemagglutinin-stimulated T-cell conditioned media (TCM) would induce NAP synthesis. Light density cells obtained from the blood of patients with chronic phase CML were depleted of T cells and monocytes. These cells were cultured with various amounts of G-CSF, GM-CSF, CSF-1, IL-1, IL-2, alpha-INF, r-INF, MoCM, GCT and TCM in a suspension culture system over 6-7 days. Evaluation of the cultures indicated that G-CSF, MoCM and GCT, but not the other factors or cytokines, consistently induced NAP synthesis in a dose-dependent manner. Actinomycin-D and puromycin in separate cultures inhibited NAP synthesis without any significant reduction in cell counts. This indicated that NAP is not prepackaged in neutrophilic cells, and its synthesis occurs by a sequential transcription at the DNA level and translation at the ribosomal level. Our results suggest that the molecule which is responsible for promotion of CFU-GM growth and differentiation along the neutrophilic cell lineage is also responsible for derepression of NAP gene and initiation of NAP synthesis.
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PMID:Granulocyte colony-stimulating factor (G-CSF) induces synthesis of alkaline phosphatase in neutrophilic granulocytes of chronic myelogenous leukemia patients. 245 37

We generated a homogeneous population of cells with cytotoxic activity termed "adherent lymphokine-activated killer" (ALAK) cells from the peripheral blood of nine patients in the chronic phase of Ph1 positive chronic myelogenous leukemia (CML). The selective enrichment of CML ALAK cells depended on their propensity to adhere to plastic and proliferate when cultured in the presence of recombinant interleukin-2 (rIL-2) for 14 days. Culture of peripheral blood mononuclear cells under these conditions resulted in growth of a uniform population of cells with morphologic characteristics of large granular lymphocytes. The NKH1+/CD3- phenotype associated with IL-2-stimulated natural killer (NK) cells was present on 79% +/- 9% of cells. Absence of colony formation in conditions promoting the growth of CFU-GEMM indicated that the CML ALAK population was not contaminated with viable hematopoietic progenitors. Cytogenetic analysis of the CML ALAK population revealed 119/120 Ph1 negative metaphases and l/120 Ph1 positive metaphase in six patients. Southern blot analysis of CML ALAK failed to demonstrate a bcr gene rearrangement in seven patients known to have a bcr gene rearrangement in myeloid cells. Comparison of ALAK populations derived from peripheral blood of CML patients and normals revealed similar cytotoxicity against the NK-sensitive K562 cell line (104 +/- 36 LU v 88 +/- 19 LU; P = NS) and the NK-resistant Raji cell line (93 +/- 26 LU v 98 +/- 28 LU; P = NS). The proliferative capacity of CML ALAK cells (101 +/- 33 fold expansion) exceeds the growth potential of the normal ALAK cells (22.3 +/- 3 fold expansion; P = .02). Direct comparison of equal numbers of CML ALAK cells and a CML LAK cell population produced by incubation of peripheral blood mononuclear cells in rIL-2 for 14 days without adherence revealed that the CML LAK population had significantly lower lytic activity against K562 and Raji cell lines. We are able to expand CML peripheral blood mononuclear cells to provide a population of ALAK cells with potent cytotoxic activity. The CML ALAK population is relatively homogeneous, not contaminated with viable stem cells, not derived from a malignant lineage, and more cytotoxic than equal numbers of CML LAK cells. Further studies are underway to determine if this ALAK population may be effective in autologous killing of chronic myelogenous leukemia stem cells.
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PMID:Adherent lymphokine-activated killer cells in chronic myelogenous leukemia: a benign cell population with potent cytotoxic activity. 247 5

Only the recent production of large amounts of highly purified recombinant interferons has made it possible to elucidate precisely the in vitro and in vivo effect of alpha- and gamma-interferon. Interferon-alpha has significantly widened the treatment modalities for some rare tumors such as hairy cell leukemia and chronic myelogenous leukemia. Although treatment results in solid tumors are disappointing, tumor regression greater than 50% is achieved in 15-25% of patients with hypernephroma or melanoma, cancers highly resistant to cytotoxic drugs. The solid tumors must be treated with high doses of interferon-alpha which causes severe side effects. Interferon-induced toxicity can be reduced by continuous subcutaneous infusion. Interferon-alpha is also used for the treatment of viral diseases such as chronic hepatitis-B, as well as for patients with AIDS and Kaposi sarcoma. Other virus infections such as herpes simplex and condylomata acuminata represent the few established indications for treatment with interferon-beta. Interferon-gamma has distinct immunomodulatory effects in vitro and in vivo, although the clinical significance of this potential has not yet been established. Thus far the treatment results in tumor patients have been poor. The future will show if the combination of interferons with other biological response modifiers, such as tumor necrosis factor or interleukin-2, or with cytotoxic drugs, brings further progress in cancer treatment.
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PMID:[Possibilities and limits of the use of interferons in the clinic]. 247 77

In 23 cases of chronic myelogenous leukemia (CML) in remission, HLA class II typing was performed by complement fixation technique on phytohemagglutin (PHA) activated lymphocytes. In 10 cases satisfactory results were obtained, whereas in 13 cases the cells were weakly or non reactive, making impossible a correct determination of HLA-DR,DQ specificities. In the 13 cases a conditioned medium containing Interleukin-2 (Il-2) and gamma interferon (IFN) was added to PHA, inducing a good HLA class II reactivity and making possible a satisfactory definition of HLA-DR,DQ specificities. The complement fixation technique on lymphocytes cultured with PHA, Il-2 and gamma IFN made possible a correct HLA-DR,DQ typing in 23 consecutive cases of CML, while such a typing is often difficult or impossible when using the microlymphocytotoxicity technique on B lymphocyte targets.
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PMID:[HLA class II typing in chronic myeloid leukemia with the complement fixation test using phytohemagglutinin-activated lymphocytes in the presence of interleukin 2 and gamma interferon]. 250 72


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