National Cancer Institute®
Last Modified: May 1, 2002
UI - 11960354
AU - Salonen MJ; Siimes MA; Salonen EM; Vaheri A; Koskiniemi M
TI - Antibody status to HHV-6 in children with leukaemia.
SO - Leukemia 2002 Apr;16(4):716-9
AD - Haartman Institute, Department of Virology, University of Helsinki, Helsinki, Finland.
Forty children with acute lymphoblastic (33) or myeloid leukaemia (seven) were studied for IgG and IgM antibodies and IgG avidity against human herpesvirus 6 (HHV-6) at the time of diagnosis, and compared with age-, sex- and season-matched children with various neurological diseases of suspected viral origin. Of the children with leukaemia, 97.5% had IgG antibodies and 40% IgM antibodies to HHV-6 compared with 92.3% and 7.7% of reference subjects (P = 0.005). A seronegative child with leukaemia seroconverted 3 weeks after the diagnosis. The avidity of IgG antibodies (based on the resistance to urea treatment) was high in all children with leukaemia. One reference child had HHV-6-specific IgG antibodies with low avidity, which together with his positive IgM indicated an acute infection. The presence of specific IgM antibodies in 40% of children with leukaemia and the high avidity of IgG suggest a reactivation or an inaproppriate primary response to HHV-6 infection. The results support the conclusion of the role of the HHV-6 infection at the onset of childhood leukaemia.
UI - 11960357
AU - Cooper MA; Caligiuri MA
TI - Immunologic manipulation in AML: from bench to bedside.
SO - Leukemia 2002 Apr;16(4):736-7
AD - Department of Internal Medicine and the Comprehensive Cancer Center, The College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA.
UI - 11960359
AU - Deguchi K; Gilliland DG
TI - Cooperativity between mutations in tyrosine kinases and in hematopoietic transcription factors in AML.
SO - Leukemia 2002 Apr;16(4):740-4
AD - Howard Hughes Medical Institute, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA.
UI - 11782470
AU - Furukawa K; Yokoyama K; Sato T; Wiels J; Hirayama Y; Ohta M; Furukawa K
TI - Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells: implication in the sensitivity to verotoxins.
SO - J Biol Chem 2002 Mar 29;277(13):11247-54
AD - Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai, Nagoya 466-0065, Japan.
Expression levels of Gb3/CD77 synthase together with Gb3/CD77 antigen were analyzed using human hematopoietic tumor cell lines and normal cells. Among about 40 kinds of cells, Burkitt lymphoma cells showed the highest gene expression concomitant with the expression levels of Gb3/CD77. Unexpectedly, megakaryoblastic leukemia lines also expressed fairly high levels of mRNA of Gb3/CD77 synthase and its product. A megakaryoblastic leukemia line, MEG-01 was sensitive to verotoxins from Escherichia coli O157 and apoptosis was induced via the caspase pathway. We also demonstrated that the cell surface Gb3/CD77 expression was reduced on differentiated MEG-01 although the mRNA level of the alpha1,4Gal-T gene increased. In this case, the localization of Gb3/CD77 was changed from the cell surface to the cytoplasm as stained with a granular pattern, co-localizing with platelet GPIIb-IIIa, indicating that some of them were platelet precursors. Small particles outside of cells also showed similar staining patterns. These results agreed with the previous report that platelets produced in mature megakaryoblasts abundantly contained Gb3/CD77 antigen. Here, we propose the possibility that verotoxins bind immature megakaryoblasts and induce their apoptosis, leading to the arrest of platelet generation in the bone marrow. This may be one of the causes of thrombocytopenia in patients with hemolytic uremic syndrome.
UI - 11996793
AU - Dubourg C; Toutain B; Helias C; Henry C; Lessard M; Le Gall JY; Le Treut
TI - A; Guenet L Evaluation of ETF1/eRF1, mapping to 5q31, as a candidate myeloid tumor suppressor gene.
SO - Cancer Genet Cytogenet 2002 Apr 1;134(1):33-7
AD - Departement de Biochimie et Biologie Moleculaire, UMR 6061, Faculte de Medecine CS 34317, 35043 Rennes Cedex, France.
Interstitial deletion of the long arm of chromosome 5 is a recurrent abnormality, mainly associated with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and it has been proposed therefore that the deleted region may contain a myeloid tumor suppressor gene. We have recently mapped a human translation termination factor gene, ETF1, to band 5q31 at D5S500, and thus to the smallest commonly deleted segment. We have evaluated ETF1 as a candidate myeloid tumor suppressor gene by analysis of the human acute myeloid leukemia cell line HL60, and of patients suffering from malignant myeloid diseases with cytogenetically-defined abnormalities of chromosome 5. Fluorescence in situ hybridization analysis revealed hemizygous loss of the ETF1 locus in HL60 cells and in four of five leukemic samples, but no inactivating mutations were identified by sequencing of the remaining ETF1 allele.
UI - 11846198
AU - Myoken Y; Sugata T; Kyo T; Fujihara M; Mikami Y
TI - Itraconazole prophylaxis for invasive gingival aspergillosis in neutropenic patients with acute leukemia.
SO - J Periodontol 2002 Jan;73(1):33-8
AD - Department of Oral Surgery, Hiroshima Red Cross and Atomic Bomb Survivors Hospital, Japan. email@example.com
BACKGROUND: Due to an increasing number of leukemic patients with invasive gingival aspergillosis during neutropenia (neutrophils <500 cells/microl for >10 days), we evaluated the efficacy of oral itraconazole prophylaxis for preventing this invasive infection at our hospital. METHODS: This was a retrospective, non-randomized study to analyze the onset of identified invasive gingival aspergillosis among 536 patients with acute leukemia at risk due to the presence of neutropenia from 1991 to 1998. Patients received itraconazole capsules levels at day 10 were measured in some patients. RESULTS: In the 39 invasive gingival aspergillosis were detected in 192 high risk patients with 469 episodes of neutropenia (7.8% of the high risk patients). 100 mg/day, there was a dramatic decrease in the infections resulting in 3 of 198 high risk patients with 511 episodes of neutropenia (1.5% of 1998, using itraconazole prophylaxis at 200 mg/day, no cases of the infection were observed in the 146 high risk patients with 380 episodes of neutropenia. The incidence of invasive gingival aspergillosis was significantly lower among patients administered itraconazole than among those without itraconazole (100 mg/day; P = 0.006 and 200 mg/day; P = 0.001). The mean itraconazole serum level in 20 patients receiving 100 mg/day was 71.78 ng/mL and in 16 patients receiving 200 mg/day was 202.67 ng/ml. CONCLUSIONS: These findings suggest that oral itraconazole could be effective for preventing invasive gingival aspergillosis in neutropenic patients with acute leukemia and warrants further randomized investigation.
UI - 11869936
AU - Di Bona E; Sartori R; Zambello R; Guercini N; Madeo D; Rodeghiero F
TI - Prognostic significance of CD56 antigen expression in acute myeloid leukemia.
SO - Haematologica 2002 Mar;87(3):250-6
AD - Department of Cellular Therapy and Hematology, Division of Hematology, San Bartolo Hospital, Vicenza, Italy. firstname.lastname@example.org
BACKGROUND AND OBJECTIVES. CD56 antigen expression has been reported in several hematologic malignancies. In acute myeloid leukemia (AML)M2 with t(8;21) and acute promyelocytic leukemia (APL) it has been found to be consistently associated with an unfavorable prognosis, whereas in other AML subtypes its role remains uncertain. We investigated CD56 expression in a cohort of AML patients in order to assess its frequency and prognostic relevance. DESIGN AND METHODS. Immunophenotypic analysis including that of CD56 antigen was available for 171 consecutive AML cells taken at diagnosis was recorded as positive when at least 20% of the cells double-stained with specific monoclonal antibodies against CD56 and CD33 antigens. RESULTS. CD56 positivity was demonstrated in 37 cases (21.6%). Its frequency was lower in M4 (6%) and higher in M5 (37%). The median percentage for CD56+ blasts was 56% (range 21-99%). CD56 positivity did not correlate with age, sex, blast count, favorable or unfavorable cytogenetics at diagnosis, nor did it influence the outcome in terms of complete remission (CR) duration (606 vs. 417 days, p=n.s.) or overall survival (OS) (210 vs. 277 days, p= n.s.). In the APL subgroup a significant difference in relapse rate was found at 3 years (71.4% in the CD56 positive group vs. 12% in the CD56 negative group, p=0.005). INTERPRETATION AND CONCLUSIONS. Our data confirm that CD56 positivity in APL patients at diagnosis is associated with a worse prognosis, suggesting that close molecular monitoring is necessary in CD56 positive APL patients. In contrast, the prognostic role of CD56 remains uncertain in the other AML subtypes.
UI - 11918536
AU - Salih HR; Starling GC; Brandl SF; Pelka-Fleischer R; Haferlach T;
TI - Hiddemann W; Kiener PA; Nuessler V Differentiation of promyelocytic leukaemia: alterations in Fas (CD95/Apo-1) and Fas ligand (CD178) expression.
SO - Br J Haematol 2002 Apr;117(1):76-85
AD - Department of Immunology, Inflammation and Pulmonary Diseases, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, USA. Helmut.Salih@md.uni-tuebingen.de
The survival of leukaemic blasts contributes to the pathological mechanism of acute promyelocytic leukaemia (APL). While treatment of APL using retinoic acid (RA) is a model of differentiation therapy, little is known about possible effects of this treatment on the Fas/FasL system. Investigation of APL cells from patients undergoing differentiation therapy with RA and of promyelocytic HL-60 and monoblastic U-937 cells cultured with RA revealed a reduction of surface expression of both Fas and its ligand. Accordingly, the sensitivity of the cells to anti-Fas-induced apoptosis decreased proportionally and the reduced expression of FasL resulted in a decreased ability of the leukaemic cells to induce apoptosis in T cells. Our findings demonstrate that there are significant changes in Fas and FasL expression during RA treatment of APL, which probably have consequences for the interaction between host immune and leukaemia cells, and thus may be involved in the beneficial effects of differentiation therapy.
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