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)

The lamins are intermediate filament proteins that form a fibrous layer at the periphery of the nucleus. Experiments in cell-free systems have suggested that mammalian lamins A and C mediate an interaction between chromatin and the inner nuclear membrane that is essential for the reformation of the nucleus after mitosis. Other investigations, however, have suggested that lamins A and C are absent from myeloid cells and myeloid leukemia cell lines. To further investigate this apparent paradox, highly sensitive Western blotting techniques were utilized in the present study to examine the expression of lamins A and C in a series of human myeloid leukemia cell lines and in bone marrow samples from patients with acute nonlymphocytic leukemia (ANLL) and chronic myelogenous leukemia. Western blotting revealed that HL-60 progranulocytic leukemia cells contained an average of 0.1 x 10(6) copies of lamins A and C per cell compared to 0.5 x 10(6) copies of lamin B1 (the quantitatively prominent human B-type lamin) per cell. During the process of phorbol ester-induced maturation to macrophages, the mRNA for lamins A and C increased in abundance, with a concomitant 4-fold increase in the average cellular content of these polypeptides. To rule out the possibility that the low but detectable levels of lamins A and C observed in untreated HL-60 cells reflected incipient maturation, the content of lamins A and C was analyzed in ANLL cell lines that do not mature toward granulocytes or monocytes. Lamins A and C were readily detected in cell lines (KG1a, HEL, Mo-7e) derived from patients with a variety of subtypes of ANLL. Expression of lamins A and C was not limited to myeloid cell lines. These polypeptides were also detectable in marrow samples from 9 of 26 patients with ANLL including at least 1 patient from each of the 5 subtypes of ANLL examined. In contrast, only 1 of 12 marrow samples from patients with aggressive phase chronic myelogenous leukemia and chronic myelogenous leukemia in blast crisis contained readily detectable lamins A and C. The implications of these findings for current hypotheses regarding the functions of the lamin polypeptides are discussed.
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PMID:Expression of nuclear envelope lamins A and C in human myeloid leukemias. 158 98

Eighty-four patients underwent allogeneic or syngeneic bone marrow transplantation as therapy for chronic myelogenous leukemia (CML) during a 5-year period at The Johns Hopkins Oncology Center. We describe the karyotype at relapse in 19 patients who were Ph chromosome positive (Ph+) at diagnosis. Eighty-four percent of patients demonstrated clonal and/or nonclonal chromosome abnormalities in addition to the t(9;22)(q34;q11) at first detection of relapse or later during relapse. These abnormalities included: Ph plus additional clonal abnormalities (three patients), Ph plus nonclonal abnormalities (five patients), Ph plus additional clonal and nonclonal abnormalities (eight patients). Three patients had only the original Ph+ clone. The additional chromosome abnormalities were primarily structural, and entirely different from those most frequently observed during karyotypic evolution in conventionally treated CML. Chromosome 1 was most frequently involved, with 1q32 being the location of three clonal and two nonclonal abnormalities. Other sites included 6p21-22 (the site of two clonal abnormalities), 7p21-22, and 10q21 (the site of two clonal and one nonclonal abnormality each). Chromosomes 5 and 7q, regions of frequent involvement in acute nonlymphocytic leukemia that follows chemotherapy for other malignancies, were infrequently involved. The clinical significance of these additional abnormalities remains undetermined at this time.
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PMID:Karyotype at relapse following allogeneic bone marrow transplantation for chronic myelogenous leukemia. 163 1

This study examined the safety and pharmacokinetic profile of a potentially therapeutic and fully human anti-CMV monoclonal antibody (SDZ MSL-109) in a phase I dose escalation trial in patients receiving allogeneic bone marrow transplants. Fifteen adult marrow transplant patients, twelve with chronic myelogenous leukemia and three with acute nonlymphocytic leukemia, in cohorts of five patients each, were administered monoclonal antibody intravenously at doses of 50, 250, and 500 micrograms/kg at approximately three-week intervals for six months. Administration of the monoclonal antibody was associated with minimal side effects and no dose-related toxicity. Antibody elimination curves in all dose groups were consistent with a two-compartment model with an alpha half-life at the low, middle, and high dose groups of 1.03, 0.82, and 0.79 days, and a beta half life of 13.9, 14.0, and 16.5 days, respectively. The volume of distribution decreased with repetitive dosing to approximate the plasma volume in each patient and the pharmacokinetic profile was comparable to that of human IgG. There was no host antiidiotypic or antiallotypic antibody formation, indicating that MSL-109 was not immunogenic. Further studies are warranted to assess the potential efficacy of human monoclonal anti-CMV disease in marrow transplant recipients and other patients with immunodeficiency disorders.
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PMID:Phase I study of safety and pharmacokinetics of a human anticytomegalovirus monoclonal antibody in allogeneic bone marrow transplant recipients. 164 4

Ten leukemic patients were treated with allogeneic bone marrow transplantation (BMT). The diagnosis were ANLL in 6 cases, CML in 3 and ALL in one. Pretransplant immuno suppressive measures including total body irradiation cyclophosphamide and daunorubicin were given. All the patients were infused with health stem cell preparation, so that the hemopoietic function was restored. Graft versus-host disease of grade I to II was present in 5 of the patients. Leukemia recurred 76 days after BMT in one patient who received the procedure during a relapse of the disease, while in the remaining 9 patients disease-free survival from 1 to 23 months has been observed.
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PMID:[Allogeneic bone marrow transplantation in the treatment of leukemia: analysis of 10 cases]. 168 16

The experience of 13 bone marrow processings is reported: 7 patients were affected by Acute Leukemias, 4 by Non Hodgkin's Lymphomas, 1 by Chronic Myelogenous Leukemia in complete remission after induction chemotherapy, 1 by Ewing's Sarcoma. Gravity sedimentation technique with 6% hydroxyethyl starch was used in all cases. A mean value of 0.754 x 10(8)/kg body weight mononuclear cells was harvested after sedimentation, with a mean recovery of 74.554%. Mean CFU-GM value was 0.543 x 10(4)/kg body weight. Only one evaluable patient, affected by ANLL, underwent Autologous Bone Marrow Transplantation and a full engraftment was noted on day +14. Results are discussed and further studies are proposed to clarify the relationship between the in vitro CFU-GM growth and the bone marrow engraftment.
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PMID:Bone marrow processing with a gravity sedimentation technique: experience of 13 cases. 169 88

Interferons (IFN) have clinical efficacy in certain hematologic malignancies. Combining IFN with conventional cytotoxic agents has been proposed as a means of improving therapy for diseases such as chronic myelogenous leukemia (CML). In this study, we examined the effect of recombinant interferons alone and in combination with Ara-C on normal and leukemic human hematopoietic progenitor cells (CFU-GM) in vitro. Mononuclear cells from normal bone marrow, peripheral blood of patients with CML, or the acute nonlymphocytic leukemia cell line HL-60 were incubated with alpha-, beta-, or gamma-IFN (0-1,000 units/ml) followed by the addition of Ara-C. The survival of normal CFU-GM was significantly increased if cells were treated with IFN 1 h before 3 h of Ara-C exposure. Similar IFN pretreatment of CML and HL-60 progenitors failed to protect leukemic CFU-GM from Ara-C-induced toxicity. This selective protection of normal CFU-GM may have clinical application.
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PMID:Interferon protects normal human granulocyte/macrophage colony-forming cells from Ara-C cytotoxicity. 170 60

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.
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PMID:Acute basophilic leukemia. A case report. 171 80

We have assessed levels of surface-expressed complement regulatory proteins, decay-accelerating factor (DAF) and membrane cofactor protein (MCP) on cells from patients with hematological malignancies. Neither malignant cells nor unaffected nucleated blood cells from the patients lacked MCP. On the other hand, complete deficiency of DAF was found in 2/10 of non-Hodgkin's lymphoma (NHL), while none of the 38 patients with acute nonlymphocytic leukemia (ANLL) (14 cases), chronic myelogenous leukemia (CML) (6 cases), acute lymphocytic leukemia (ALL) (12 cases) and chronic lymphocytic leukemia (CLL) (6 cases) lacked DAF. The two patients with DAF-negative NHL had no history of paroxysmal nocturnal hemoglobinuria (PNH), and their peripheral blood cells were DAF-positive. One DAF-negative NHL exhibited T cell markers and the other those of B cell. In both cases, treatment of the DAF-negative lymphoma cells with antibody against MCP (M177) followed by Mg(2+)-EGTA-serum resulted in efficient deposition of homologous C3. These results infer that some NHL specifically lack DAF and, through treatment with M177, are targeted by homologous C3.
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PMID:Deficiency of complement decay-accelerating factor (DAF, CD55) in non-Hodgkin's lymphoma. 172 75

Two cases are described with the rare combination of inv(16)(p13q22), strongly associated with acute myelomonocytic leukemia with eosinophilia, M4Eo, and the Philadelphia translocation, t(9;22)(q34;q11), hallmark of chronic myeloid leukemia (CML) and rarely found, (less than 1%), in acute nonlymphocytic leukemia. The patients were: case 1, a 9-year-old girl presenting with a white blood cell count (WBC) 42 x 10(9)/L with 32% blasts and bone marrow with blasts and eosinophil precursors consistent with M4Eo, and case 2, a 25-year-old man with WBC 34.7 x 10(9)/L with 13% blasts and bone marrow with features of M4Eo and basophilia. Both patients achieved remission but died following bone marrow transplantation in first remission (case 1) or in relapse (case 2). Cytogenetic findings were: case 1, at diagnosis, 46,XX,inv(16)(p13q22)(21)/46,XX,t(9;22) (q34;q11),inv(16)(8)/46,XX(10), and case 2, at diagnosis, 46,XY,t(9;22) (q34;q11),inv(16)(p13q22) (16) and in remission, 46,XY,t(9;22)(q34;q11) (1)/46,XY (24). Investigation of the breakpoint on 22 in case 1 with Southern blotting and the polymerase chain reaction demonstrated the presence of a p190 mRNA and a breakpoint typical of acute leukemia. Thus a diagnosis of M4Eo was supported by clinical and cytogenetic sequelae in each case; the Ph in case 1 was apparently secondary to inv(16), in case 2 the Ph probably preceded inv(16) in the etiology of the leukemia.
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PMID:Inversion of chromosome 16 with the Philadelphia chromosome in acute myelomonocytic leukemia with eosinophilia. Report of two cases. 172 47

A case of trisomy 13 is presented: a 73-year-old man with acute nonlymphocytic leukemia (ANLL), FAB borderline M1/M2, and peripheral leukocyte and platelet counts that were difficult to control with chemotherapy. A literature review shows that 35 cases of trisomy 13 are known at present. They are characterized by male predominance (76%), preferentially myeloid disorders (ANLL, myelodysplastic syndromes, chronic myeloid leukemia), leucocytosis, and relatively high platelet counts and hemoglobins. It is suggested that trisomy 13 is a specific nosologic entity with male predominance and characterized by interference with proliferation and differentiation in the myeloid differentiation series.
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PMID:Trisomy 13: a preferentially male chromosome aberration interfering specifically with myeloid proliferation and differentiation? Report of a case and review of the literature. 175 88


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