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)

In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony-stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the "autonomous" colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder.
Blood 1991 Sep 15
PMID:Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity. 171 91

A case of acute nonlymphocytic leukemia (ANLL) with primitive basophilic differentiation is presented. The patient had no antecedent history or concomitant presence of chronic myelogenous leukemia. The leukemic blasts constituted 83% of the peripheral white blood cells and more than 90% of the marrow nucleated cells. Cytoplasmic vacuoles were found in some leukemic cells. About half the leukemic cells showed a few azurophilic granules stained with Wright's stain, whereas exhibited a faint pinkish hue around the cells without cytoplasmic granules (water-soluble granules) by Riu's stain. The cytoplasmic granules failed to be stained with peroxidase but stained positively with toluidine blue. The former result could lead one to misclassify the case as lymphoid leukemia, but the characteristic finding of basophilic cells in Riu's stain should direct one to make the diagnosis of ANLL with basophilic differentiation. The cytochemical findings of this case suggested that basophilic differentiation should be considered when leukemic cells show peroxidase-negative granules. Riu's stain and toluidine blue stain are useful to make the correct diagnosis.
Changgeng Yi Xue Za Zhi 1991 Sep
PMID:Acute basophilic leukemia. A case report. 171 80

A modified version of the original reported panning technique was used to separate CD34+ cells from the peripheral blood of patients with chronic myeloid leukemia (CML). In 13 out of 23 separations, populations of cells were obtained in which CD34+ cells constituted greater than 50% of the cells present. The best recovery and enrichment of the CD34+ cells was achieved when cells were obtained from patients in the accelerated phase of CML, when the cells were processed on the same day they were obtained from patients, and when adherence to soybean agglutinin flasks was used as a pre-enrichment step. In suspension culture, the CD34+ cells were capable of extensive proliferation and differentiation. In semi-solid culture, the number of colony-forming units (CFUs) directly correlated with CD34 positivity. The number of clonogenic cells/CD34+ cells was highest at the time of initial diagnosis of CML, fell during the chronic phase (CP) of the disease, and rose at the time of disease acceleration. This observation suggests that therapy during the CP of the disease produces a greater reduction in clonogenic cells than in the number of CD34+ cells. This effect disappears at the time of disease acceleration, presumably because of the development of drug resistance in the clonogenic cells.
Int J Cell Cloning 1991 Sep
PMID:Isolation and characterization of the CD34+ hematopoietic progenitor cells from the peripheral blood of patients with chronic myeloid leukemia. 172 Jan 55

In a pilot study, 32 patients with Philadelphia chromosome-positive chronic myelogenous leukemia were treated with intensive chemotherapy induction followed by interferon-alpha (IFN-A) maintenance. Intensive chemotherapy consisted of three cycles of daunorubicin 120 mg/m2 on day 1, cytarabine 80 mg/m2 daily for 10 days, vincristine 2 mg on day 1, and prednisone 100 mg daily for 5 days (DOAP). Maintenance therapy with IFN-A at a doses of 3 x 10(6) to 5 x 10(6) units/m2 daily was adjusted according to counts and toxicity. The outcome of patients was compared with a matched historic population of 64 patients treated with IFN-A alone. Overall, 60% of patients had a cytogenetic response (partial or complete) with induction chemotherapy, but only eight (25%) had a sustained cytogenetic response with IFN-A maintenance. After a median follow-up of 67 months, the 6-year survival rate of the 32 patients was 58%, compared with 36% for the matched historic group (P = 0.084). The incidence of lymphoid blastic transformation in the two groups was 25% and 48%, respectively (P = 0.10) and durable cytogenetic responses, 25% and 19%, respectively (P = 0.48). In summary, the addition of intensive chemotherapy induction to IFN-A maintenance does not improve the survival rate, incidence of lymphoid blastic transformation, or incidence of durable cytogenetic response compared with the results achieved with IFN-A therapy alone.
Cancer 1991 Sep 15
PMID:Intensive chemotherapy induction followed by interferon-alpha maintenance in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. 187 71

Two forms of activated BCR/ABL proteins, P210 and P185, that differ in BCR-derived sequences, are associated with Philadelphia chromosome-positive leukemias. One of these diseases is chronic myelogenous leukemia, an indolent disease arising in hematopoietic stem cells that is almost always associated with the P210 form of BCR/ABL. Acute lymphocytic leukemia, a more aggressive malignancy, can be associated with both forms of BCR/ABL. While it is virtually certain that BCR/ABL plays a central role in both of these diseases, the features that determine the association of a particular form with a given disease have not been elucidated. We have used the bone marrow reconstitution leukemogenesis model to test the hypothesis that BCR sequences influence the ability of activated ABL to transform different types of hematopoietic cells. Our studies reveal that both P185 and P210 induce a similar spectrum of hematological diseases, including granulocytic, myelomonocytic, and lymphocytic leukemias. Despite the similarity of the disease patterns, animals given P185-infected marrow developed a more aggressive disease after a shorter latent period than those given P210-infected marrow. These data demonstrate that the structure of the BCR/ABL oncoprotein does not affect the type of disease induced by each form of the oncogene but does control the potency of the oncogenic signal.
Mol Cell Biol 1991 Sep
PMID:Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. 187 48

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.
Blood 1991 Sep 15
PMID:Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. 188 23

We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage.
Blood 1991 Sep 15
PMID:VpreB gene expression in hematopoietic malignancies: a lineage- and stage-restricted marker for B-cell precursor leukemias. 188 24

The concomitant occurrence of pregnancy and chronic myeloid leukemia is uncommon. The use of hydroxyurea in chronic myeloid leukemia during pregnancy is unknown. We report on a patient with chronic myeloid leukemia in whom hydroxyurea was used during pregnancy with a successful outcome for both mother and fetus.
Am J Obstet Gynecol 1991 Sep
PMID:Use of hydroxyurea in chronic myeloid leukemia during pregnancy: a case report. 161 1

A patient who developed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) 5 years after successful treatment for thyroid carcinoma, is reported. The Philadelphia chromosome was the typical 9;22 translocation. Southern blot analysis showed breakpoint cluster region rearrangement as observed in classical CML. Up to now, only two cases of CML have been reported following treatment for thyroid carcinoma. This rare complication has also been described after therapy for other malignancies. At present, it is not clear whether the development of CML after thyroid carcinoma represents a therapy-induced complication, a coincidence, or an increased susceptibility to secondary malignancies due to the malignant process itself.
Cancer Genet Cytogenet 1991 Sep
PMID:Chronic myelogenous leukemia after treatment with 131I for thyroid carcinoma. Report of a case and review of the literature. 193 23

The development of cancer is generally believed to occur by a multistep process in which critical genetic defects accumulate in a clone of cells, confer a growth advantage, and result in the emergence of more malignant subclones. This paper describes the clonal origin of cells in a patient with Philadelphia-chromosome negative, M-bcr rearrangement-positive chronic myelogenous leukemia, observed in two episodes of lymphoid blast crisis (BC), the intervening chronic phases (CP), and following allogeneic bone marrow transplantation. Serial analysis of immunoglobulin heavy and kappa light chain (IgJH, IgCK), beta-T-cell receptor (beta-TcR) and bcr major breakpoint cluster region (M-bcr) gene rearrangements was performed. Clonal IgJH rearrangements present in cells of the first lymphoblastic crisis (BC1) were altered during the chronic phase post-treatment (CP1), and were again altered in recurrent blast crisis (BC2). In addition, the M-bcr gene rearrangement present in BC1 and CP1 was absent from cells in BC2. These observations suggest that the course of clinical neoplastic disorders may not always be characterized simply by a hierarchical process of clonal evolution, but may also involve clonal succession of malignant cells. Moreover, the deletion of M-bcr in recurrent BC suggests that bcr/abl may not be essential for the maintenance of cell growth in established BC.
Leukemia 1991 Sep
PMID:Clonal succession and deletion of bcr/abl sequences in chronic myelogenous leukemia with recurrent lymphoid blast crisis. 194 28


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