National Cancer Institute®
Last Modified: March 1, 2002
UI - 11805585
AU - Soderberg KC; Naumburg E; Anger G; Cnattingius S; Ekbom A; Feychting M
TI - Childhood leukemia and magnetic fields in infant incubators.
SO - Epidemiology 2002 Jan;13(1):45-9
AD - Institute of Environmental Medicine, Karolinska Institutet, Institute, Stockholm, Sweden. Karin.Soderberg@imm.ki.se
In studies of magnetic field exposure and childhood leukemia, power lines and other electrical installations close to the children's homes constitute the most extensively studied source of exposure. We conducted a study to assess whether exposure to magnetic fields in infant incubators is associated with an increased leukemia risk. We identified all children with leukemia born in Sweden between 1973 and 1989 from the national Cancer Registry and selected at random one control per case, individually matched by sex and time of birth, from the study base. We retrieved information about treatment in infant incubators from medical records. We made measurements of the magnetic fields inside the incubators for each incubator model kept by the hospitals. Exposure assessment was based on measurements of the magnetic field level inside the incubator, as well as on the length of treatment. For acute lymphoblastic leukemia, the risk estimates were close to unity for all exposure definitions. For acute myeloid leukemia, we found a slightly elevated risk, but with wide confidence intervals and with no indication of dose response. Overall, our results give little evidence that exposure to magnetic fields inside infant incubators is associated with an increased risk of childhood leukemia.
UI - 11843814
AU - Matsushima T; Saitoh T; Karasawa M; Takizawa M; Miyawaki S; Nojima Y;
TI - Murakami H Effect of cytokines on growth and differentiation of leukaemic cells with translocation t(6;9)(p23;q34).
SO - Br J Haematol 2001 Dec;115(4):812-6
AD - Third Department of Internal Medicine, Gunma University School of Medicine, Shouwa-machi 3-39-15, Maebashi, Gunma 371-0034, Japan. email@example.com
The translocation t(6;9)(p23;q34) is detected infrequently in subtypes of haematological malignancies including acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). Although the t(6;9) leukaemia is commonly associated with bone marrow basophilia, the cytological characteristics of leukaemic cells are unclear. In the current study, we examined the in vitro effects of several cytokines on growth and differentiation of t(6;9) leukaemic cells. Isolated bone marrow mononuclear cells from four patients with t(6;9) (two MDS and two AML) were cultured for 14 d in the presence or absence of each cytokine. At the end of culture, viable cells were counted, and their histology was examined. Bone marrow cells obtained from 22 patients (10 AML, six AML from MDS, six MDS) lacking t(6;9) were used as controls. Compared with control cultures, significantly higher numbers of blasts appeared in the culture of bone marrow cells from t(6;9)-positive patients in response to stimulation with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) or interleukin 3 (IL-3). Stem cell factor (SCF) had little effect. Neutrophil counts were also significantly increased in the presence of G-CSF or IL-3. SCF and IL-3 were potent in increasing basophil counts from t(6;9)-positive cultures. These findings suggest that bone marrow cells obtained from t(6;9) patients are highly sensitive to growth- and/or differentiation-promoting cytokines. Special attention should be paid to the use of "therapeutic" cytokines in these patients.
UI - 11807007
AU - Zhu Q; Zhang JW; Zhu HQ; Shen YL; Flexor M; Jia PM; Yu Y; Cai X; Waxman
TI - S; Lanotte M; Chen SJ; Chen Z; Tong JH Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk.
SO - Blood 2002 Feb 1;99(3):1014-22
AD - Shanghai Institute of Hematology and Key Laboratory for Human Genome Research, Rui Jin Hospital, Shanghai Second Medical University, 197 Rui Jin Road II, Shanghai 200025, P.R. China.
Acute promyelocytic leukemia (APL) is characterized by the specific chromosome translocation t(15;17) with promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) fusion gene and the ability to undergo terminal differentiation as an effect of all-trans retinoic acid (ATRA). Recently, arsenic trioxide (As(2)O(3)) has been identified as an alternative therapy in patients with both ATRA-sensitive and ATRA-resistant APL. At the cellular level, As(2)O(3) triggers apoptosis and a partial differentiation of APL cells in a dose-dependent manner; both effects are observed in vivo among patients with APL and APL animal models. To further explore the mechanism of As(2)O(3)-induced differentiation, the combined effects of arsenic and a number of other differentiation inducers on APL cell lines (NB4 and NB4-R1) and some fresh APL cells were examined. The data show that a strong synergy exists between a low concentration of As(2)O(3) (0.25 microM) and the cyclic adenosine monophosphate (cAMP) analogue, 8-CPT-cAMP, in fully inducing differentiation of NB4, NB4-R1, and fresh APL cells. Furthermore, cAMP facilitated the degradation of As(2)O(3)-mediated fusion protein PML-RARalpha, a process considered to play a key role in overcoming the differentiation arrest of APL cells. On the other hand, cAMP could significantly inhibit cell growth by modulating several major players in G(1)/S transition regulation. Interestingly, H89, an antagonist of protein kinase A, could block the differentiation-inducing effect of As(2)O(3) potentiated by cAMP. These results thus support the existence of a novel signaling cross-talk for APL maturation, which may deepen understanding of As(2)O(3)-induced differentiation in vivo, and thus furnish insights for new therapeutic strategies.
UI - 11806982
AU - Latagliata R; Petti MC; Fenu S; Mancini M; Spiriti MA; Breccia M;
TI - Brunetti GA; Avvisati G; Lo Coco F; Mandelli F Therapy-related myelodysplastic syndrome-acute myelogenous leukemia in patients treated for acute promyelocytic leukemia: an emerging problem.
SO - Blood 2002 Feb 1;99(3):822-4
AD - Department of Human Biotechnologies and Hematology, University La Sapienza of Rome, Cattedra di Ematologia, Via Benevento 6-00161, Rome, Italy. firstname.lastname@example.org
The use of all-trans retinoic acid (ATRA) in combination with chemotherapy has markedly improved the prognosis for patients with acute promyelocytic leukemia (APL); the higher complete remission (CR) and survival rates now reported in this disease almost approach those obtained for other highly curable hematologic malignancies. Of 77 patients with APL who were consecutively treated at a single institution and who achieved CR after induction and consolidation therapy, 5 (6.5%) acquired therapy-related myelodysplasia (tMDS), acute myelogenous leukemia (AML), or both (tMDS-AML). Of these, 3 of 46 (6.5%) patients received front-line chemotherapy with or without ATRA and acquired tMDS-AML while in first remission of APL. Two underwent repeated chemotherapy cycles with ATRA because of APL relapse and acquired tMDS-AML while in the second or third remission of APL. In 2 patients, clinical and biologic characteristics of tMDS-AML were as expected for postalkylating forms (long latency, MDS phase preceding AML, karyotypic aberrations involving chromosomes 5 or 7), even though one of them had not previously received alkylating drugs. Three of the 5 patients died shortly after tMDS-AML diagnosis, one is alive with tMDS, and one is alive and in CR after allogeneic bone marrow transplantation. The occurrence of tMDS-AML after successful therapy for APL is an emerging problem. The availability of prognostic score systems at initial diagnosis and monitoring of residual disease by polymerase chain reaction might allow better tailoring of treatment intensity in APL to spare unnecessary toxicity and to minimize the risk for tMDS-AML in patients who are presumably cured.
UI - 11841408
AU - Ohara A; Kojima S; Okamura J; Inada H; Kigasawa H; Hibi S; Tsukimoto I;
TI - Aplastic Anaemia Committee of the Japanese Society of Pediatric Haematology Evolution of myelodysplastic syndrome and acute myelogenous leukaemia in children with hepatitis-associated aplastic anaemia.
SO - Br J Haematol 2002 Jan;116(1):151-4
AD - First Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan. email@example.com
In hepatitis-associated aplastic anaemia (HAA), an immune-mediated mechanism is solely responsible for the development of pancytopenia. We retrospectively analysed the clinical outcome of 61 children with HAA, diagnosed between 1988 and 1996. Of 61 patients, 41 did not receive bone marrow transplantation (BMT) and their survival rate at 7 years was 61.4 +/- 9.3%(+/- SE). Five of these 41 patients developed myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML) 7-57 months after the diagnosis of HAA. The incidence of MDS/AML in severe HAA patients who did not receive BMT (n = 30, 27.0 +/- 10.8%) appeared to be similar to that of severe idiopathic AA patients (n = 155, 14.7 +/- 3.7%) treated in the same period.
UI - 11665752
AU - Kaminska T; Hus I; Dmoszynska A; Kandefer-Szerszen M
TI - Effect of granulocyte-macrophage colony-stimulating growth factor on interferon and tumor necrosis factor production in whole blood cell cultures of patients with acute myelogenous leukemia.
SO - Arch Immunol Ther Exp (Warsz) 2001;49 Suppl 2():S83-7
AD - Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, Lublin, Poland.
The effect of recombinat human granulocyte-macrophage colony-stimulating growth factor (rHuGM-CSF) treatment on in vitro interferon (IFN) and tumor necrosis factor (TNF) production in peripheral blood cells of 46 patients with acute myelogenous leukemia (AML) was examined. GM-CSF significantly enhanced virus-induced IFN-alpha production in blood cells (containing 68% of blasts) of 28 patients with M4-M5 AML according to the French-American-British (FAB) classification and also phytohemagglutinin (PHA)-induced IFN-gamma production in blood cells (containing 70% of blasts) of 18 patients with AML MO-M3 type. In control blood cells (25 healthy persons) GM-CSF enhanced PHA-induced IFN-gamma but did not influence IFN-alpha production. In the presence of GM-CSF, TNF-alpha titers induced with lipopolysaccharide were also higher in control blood cells but not in cells of patients with M0-M3 or M4-M5 type of AML. The significance of GM-CSF-enhanced IFN-alpha and IFN-gamma production in antimicrobial and anti-leukemic immune reactions which can develop during GM-CSF therapy is discussed.
UI - 11840291
AU - Srinivasa SP; Doshi PD
TI - Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways cooperate in mediating cytokine-induced proliferation of a leukemic cell line.
SO - Leukemia 2002 Feb;16(2):244-53
AD - Pharmacia Discovery Research, 700 Chesterfield Parkway North, St. Louis, MO 63198, USA.
Granulocyte colony-stimulating factor (G-CSF) and fetal liver tyrosine kinase-3 (Flt3) ligand (FL) act in synergy to induce expansion and mobilization of hematopoietic progenitor cells. Regulation of mitogen activated protein (MAP) kinase pathways and gene transcription, induced by these cytokines were examined using the OCI-AML5 cell line. For this purpose, FL and G-CSF were used either alone, or in combination as the co-addition of FL and G-CSF (FL+G-CSF), or a chimeric molecule, progenipoietin-1 (ProGP-1). Both G-CSF and FL induced phosphorylation of extracellular signal-regulated kinases (ERKs) while p38 mitogen activated protein (MAP) kinase was phosphorylated only in response to G-CSF but not FL. Studies using specific kinase inhibitors suggested that both ERK and p38 MAP kinase pathways were required for the optimal cell proliferation in response to both G-CSF and FL. The magnitude of activation of the ERK pathway and induction of genes involved in cell cycle progression by G-CSF and FL exhibited a strong correlation with the degree of cell proliferation. These data suggest that OCI-AML5 cells proliferate at least in part, due to the activation of both ERK and p38 MAP kinase pathways in response to G-CSF and FL. This study represents the first report of the specific cell cycle genes induced by FL.
UI - 11857012
AU - Moorman AV; Roman E; Cartwright RA; Morgan GJ
TI - Smoking and the risk of acute myeloid leukaemia in cytogenetic subgroups.
SO - Br J Cancer 2002 Jan 7;86(1):60-2
AD - Leukaemia Research Fund Centre for Clinical Epidemiology, University of Leeds, 30 Hyde Terrace, Leeds LS2 9LN, UK. firstname.lastname@example.org
Cytogenetically-defined subgroups of acute myeloid leukaemia have distinct biologies, clinical features and outcomes. Evidence from therapy-related leukaemia suggests that chromosomal abnormalities are also markers of exposure. Our results suggest that the smoking-associated risk for acute myeloid leukaemia is restricted to the t(8;21)(q22;q22) subgroup. This supports the hypothesis that distinct cytogenetic subgroups of acute myeloid leukaemia have separate aetiologies.
UI - 11721386
AU - Ma D; Sun Y; Ma X
TI - [Sodium arsenite selectively inducing apoptosis of G2 + M phase NB4 cells]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Jun;20(6):296-9
AD - General Hospital of Shenyang Military Area, Shenyang 110015.
OBJECTIVE: To explore the mechanism of sodium arsenite inducing apoptosis of NB4 cells. METHODS: The apoptosis of NB4 cells was studied by flow cytometry, DNA gel electrophoresis and Western blot analysis. RESULTS: 1. Sodium arsenite induced apoptosis of NB4 cells while the cells were arrested in G2 + M phase; 2. dUTP-FITC specifically labeled NB4 cells in G2 + M phase after the cells were treated with sodium arsenite; 3. After the treatment the expressions of cyclin A, E, D1, D2 and D3 of the NB4 cells did not change significantly, while the expression of cyclin B1 was up-regulated with prolongation of the treatment; 4. Some of S phase NB4 cells expressed high level cyclin B1 during the early period of treatment (16 h), but most of NB4 cells expressing high level of cyclin B1 were in G2 + M phase. CONCLUSION: Sodium arsenite selectively induced apoptosis of G2 + M phase NB4 cells, accompanied by upregulation of cyclin B1.
UI - 11721388
AU - Chen Y; Miao J; Zhu X
TI - [Design and synthesis of anti-PML-RAR alpha antisense and its effects on the growth and apoptosis of NB4 cells]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Jun;20(6):303-6
AD - Shanghai Institute of Hematology, Laboratory of Leukemia Research, Renji Hospital, Shanghai Second Medical University, Shanghai 200001.
OBJECTIVE: To synthesize antisense oligodeoxynucleotides (AS) targeting the fusion point region (FUAS) and the start codon region (STAS) of the long type PML-RAR alpha mRNA and investigate its stability, specificity and effects on the growth and apoptosis of NB4 cells. METHODS: NB4 cell apoptosis was assayed by flow cytometry, cell-fluorescence and DNA gel electrophoresis. Trypan blue exclusion was used for cell counts, and polyacrylamide gel electrophoresis for oligodeoxynucleotides. RESULTS: The synthesized 18 bp phosphorothioate oligodeoxynucleotides was stable, resistant to nuclease, and no unspecific effects. Both STAS and FUAS could inhibit the NB4 cell growth in a dose-dependent manner. Low concentration (20 micrograms/ml) of STAS or FUAS resulted in growth inhibition of 0%-11.3%, and the highest inhibition was found at concentration of 80 micrograms/ml (inhibition rate 50.0%-67.7%). Cell DNA content analyzed by flow cytometry showed the typical profile of apoptotic cells at 7th day, 9th day of treatment with FUAS. Percentages of apoptotic cells in FUAS-treated cells was 9.3%, 24.5%, 41.0% and 34.2% after 3, 5, 7 and 9 days of FUAS treatment, respectively. CONCLUSION: STAS and FUAS successfully synthesized and both of them could inhibit the growth and induce the cell apoptosis of NB4 cells.
UI - 11721389
AU - Chen Y; Miao J; Zhu X
TI - [Effects of anti-PML-RAR alpha antisense on cell morphology and expression of PML-RAR alpha mRNA and protein of NB4 cells]
SO - Zhonghua Xue Ye Xue Za Zhi 1999 Jun;20(6):307-9
AD - Shanghai Institute of Hematology, Renji Hospital, Shanghai Second Medical University, Shanghai 200001.
OBJECTIVE: To investigate the effects of anti-PML-RAR alpha antisense (FUAS) on cell morphology, expression of PML-RAR alpha mRNA and PML-RAR alpha/PML protein localization of NB4 cells. METHODS: PML-RAR alpha mRNA expression was assayed by RT-PCR and PML-RAR alpha/PML protein localization by immuno-fluorescence. RESULTS: NB4 cells were partially differentiated after 5 days of FUAS treatment and typical apoptosis was found after 7 days incubation with FUAS. The expression of PML-RAR alpha mRNA at 24 h was already down regulated in FUAS-treated cells. After 24 h, 72 h and 120 h incubation with FUAS, PML-RAR alpha mRNA showed 52.0%, 68.7% and 23.4% reductions, respectively, as compared with that of control. Immuno-fluorescence analysis with anti-PML monoclonal antibody showed disappearance of microgranules, residual granules becoming larger discrete dots at 24 h of FUAS treatment and almost disappearence of dots at 120 h. CONCLUSION: FUAS specifically blocks the expression and translation of PML-RAR alpha gene, makes the production of PML-RAR alpha fusion protein decrease or disappear and prompts cell differentiation.
UI - 11840268
AU - Marone M; Scambia G; Bonanno G; Rutella S; de Ritis D; Guidi F; Leone G;
TI - Pierelli L Transforming growth factor-beta1 transcriptionally activates CD34 and prevents induced differentiation of TF-1 cells in the absence of any cell-cycle effects.
SO - Leukemia 2002 Jan;16(1):94-105
AD - Dept of Gynecology, Catholic University, Rome Italy.
A number of cytokines modulate self-renewal and differentiation of hematopoietic elements. Among these is transforming growth factor beta1 (TGF-beta1), which regulates cell cycle and differentiation of hematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has been previously shown by us and other authors that TGF-beta1 maintains human CD34(+) hematopoietic progenitors in an undifferentiated state, independently of any cell cycle effects, and that depletion of TGF-beta1 triggers differentiation accompanied by a decrease in CD34 antigen expression. In the present work, we show that exogenous TGF-beta1 upregulates the human CD34 antigen in the CD34(+) cell lines TF-1 and KG-1a, but not in the more differentiated CD34(-) cell lines HL-60 and K-562. We further studied this effect in the pluripotent erythroleukemia cell line TF-1. Here, TGF-beta1 did not effect cell growth, but induced transcriptional activation of full-length CD34 and prevented differentiation induced by differentiating agents. This effect was associated with nuclear translocation of Smad-2, activation of TAK-1, and with a dramatic decrease in p38 phosphorylation. In other systems TGF-beta1 has been shown to activate a TGF-beta-activated kinase 1 (TAK1), which in turn, activates p38. The specific inhibitor of p38 phosphorylation, SB202190, also increased CD34 RNA expression, indicating the existence of a link between p-38 inhibition by TGF-beta1 and CD34 overexpression. Our data demonstrate that TGF-beta1 transcriptionally activates CD34 and prevents differentiation of TF-1 cells by acting independently through the Smad, TAK1 and p38 pathways, and thus provide important clues for the understanding of hematopoietic development and a potential tool to modify response of hematopoietic cells to mitogens or differentiating agents.
UI - 11224485
AU - Chillon CM; Garcia-Sanz R; Balanzategui A; Ramos F; Fernandez-Calvo J;
TI - Rodriguez MJ; Rodriguez-Salazar MI; Corrales A; Calmuntia MJ; Orfao A; Gonzalez M; San Miguel JF Molecular characterization of acute myeloblastic leukemia according to the new WHO classification: a different distribution in Central-West Spain.
SO - Haematologica 2001 Feb;86(2):162-6
AD - Department of Hematology, University Hospital of Salamanca, Paseo de San Vicente, 58-182, Salamanca 37007, Spain.
BACKGROUND AND OBJECTIVES: Molecular analysis has contributed to the identification of several non-random chromosomal translocations, such as t(15;17), t(8:21), inv(16)/t(16;16) and 11q23 abnormalities, typically associated with acute myeloid leukemia (AML). The identification of these chromosomal abnormalities helps not only to define different AML subtypes with distinct prognoses and treatments but also to monitor the disappearance of malignant cells after treatment. Recent reports suggest that the frequency of these alterations may differ according to geographic distribution. However, most of these reports focus on just one or two genetic alterations, which may lead to some selection bias. Appropriate epidemiological studies should be based on unselected consecutive series of patients in which all relevant genes are simultaneously analyzed. The aim of the present study was to explore whether or not the incidence of genetic lesions in Spanish AML patients differs from that reported in other countries. DESIGN AND METHODS: In a series of 145 consecutive un-selected adult patients with AML we simultaneously analyzed the presence of 4 genetic abnormalities, PML/RARalpha for t(15;17), AML1/ETO for t(8;21), CBFbeta/MYH11 for inv(16)/t(16;16) and rearrangements of the MLL gene for 11q23 abnormalities. AML were classified using the new World Health Organization (WHO) classification for hematologic malignancies. The techniques used were standardized according to the recommendations of the European BIOMED-1 Concerted Action. RESULTS: The PML/RARalpha transcript was present in 34 patients (23.4%) (23 were bcr1, 2 bcr2 and 9 bcr3). The AML1/ETO fusion transcript was detected in only 2 cases (1.4%) both with M2 morphology, but 29 other cases with M2 morphology were negative. CBFbeta/MYH11 transcript was present in 9 cases (6.2%) eight of them displaying M4Eo morphology. Finally, 5 cases (3.5%) showed rearrangements of theMLL gene. Our results differ from those reported from the United States and North/Central Europe, particularly regarding the incidence of t(15;17) and t(8;21) translocations. In Spain the frequency of t(15;17) is higher while that of t(8;21) is lower. INTERPRETATION AND CONCLUSIONS: These data add epidemiological information about geographic heterogeneity of such chromosome aberrations in AML and would contribute to the design of specific screening strategies adapted to the incidence in each country.
UI - 11706877
AU - Milligan DW
TI - The diagnosis and management of acute myeloid leukaemia.
SO - Clin Med 2001 Sep-Oct;1(5):358-61
AD - Birmingham Heartlands Hospital. email@example.com
Significant advances have been made in the management of AML in younger patients in the last 20 years, and it is easier to identify individual risk groups and stratify treatment accordingly. Results remain discouraging in the elderly, except for the minority with favourable risk factors, and new approaches are needed for most of these patients.
UI - 11523415
AU - Ol'shanskaia IuV; Udovichenko AI; Vodinskaia LA; Savchenko VG;
TI - Domracheva EV [Constitutional pericentric inversions of chromosomes 5, 7 and 9 in patients with myeloid tumors]
SO - Ter Arkh 2001;73(7):68-70
UI - 11694950
AU - Estey E
TI - Reducing mortality associated with immediate treatment complications of adult leukemias.
SO - Semin Hematol 2001 Oct;38(4 Suppl 10):32-7
AD - Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Analysis of data from 806 patients with newly diagnosed adult acute myelocytic leukemia (AML) (not including acute promyelocytic leukemia [APL] patients) treated at M.D. Anderson Cancer Center from 1995 through 1999 indicated that among patients entering a particular week of induction therapy, mortality rates were 6%, 8%, 6%, 9%, and 6% during weeks 1 to 2, 3 to 4, 5 to 6, 7 to 8, and 9 to 10, respectively. Because the mortality rate was not higher in the period immediately after treatment began, a definition of the period covered by the term "immediate" is somewhat arbitrary rather than "biologic," as might be the case if the early weeks were distinguished by a particularly high mortality rate. M.D. Anderson researchers have focused on the treatment complications and deaths occurring in the first 4 weeks after the beginning of induction therapy. In the first week, infection contributed to 71% of the deaths and pulmonary hemorrhage associated with diffuse alveolar damage contributed to 44%; the incidence of infection rose while the incidence of hemorrhage decreased during weeks 2 to 4. The associations between 4-week mortality rates with age, performance status, and white blood cell (WBC) count are well known. Study data suggest that elevated pretreatment levels of uric acid and tumor necrosis factor-alpha (TNF-alpha) levels are similarly associated with 4-week mortality. The prognostic significance of hyperuricemia appears independent of WBC, creatinine, and TNF-alpha. M.D. Anderson investigators have studied the roles of pheresis, TNF-alpha receptor-blocking agents, continuous venovenous dialysis, and newer antifungal agents in reducing early mortality. In particular, data from a retrospective M.D. Anderson analysis of pheresis (146 patients with WBC > 50,000 +/- microL) suggest that the value of this procedure is questionable. Preliminary data also point to the potential value of the TNF-alpha alpha receptor blocker etanercept (Enbrel, Immunex Corp, Seattle, WA) in patients at high risk of early death. Data from a randomized M.D. Anderson trial suggest that oral fluconazole plus itraconazole capsules are equivalent to liposomal amphotericin in antifungal prophylaxis. Because neither alternative appears satisfactory, researchers at M.D. Anderson are examining the role of intravenous itraconazole, which produces higher concentrations than itraconazole capsules in prophylaxis, and the role of FK 463 in treatment of fungal infections. Copyright 2001 by W.B. Saunders Company.
UI - 11855149
AU - Liu L; Sun B; Liang Y
TI - [Analysis of telomerase activity and telomere length in acute myelogenous leukemia]
SO - Zhonghua Xue Ye Xue Za Zhi 2001 Nov;22(11):592-4
AD - Department of Hematology, Tangdu Hospital, Fourth Millitary Medical University, Xi'an 710038, China.
OBJECTIVE: To study the changes and significance of telomerase activity and telomere length in acute myelogenous leukemia. METHODS: TRAP-ELISA-PAGE was used to detect telomerase activity, Southern blot to estimate the length of telomere. RESULTS: Telomerase activity was significantly higher in AML(Absorption(A): 2.298 +/- 1.059) than in normal control(A: 0.387 +/- 0.598) and the mean telomere length of AML [(7.6 +/- 2.1) kb] was significantly shorter than that of normal control[(9.3 +/- 1.9) kb]. The alteration of the telomere length was detected mainly in telomerase-positive AML. CONCLUSIONS: It suggested that there was a close relationship between telomerase activity and telomere length in AML. The activation of telomerase might play an important role in the genesis and development of AML and telomere length changes may correlate with the activation of telomerase.
UI - 11369655
AU - Stirewalt DL; Kopecky KJ; Meshinchi S; Appelbaum FR; Slovak ML; Willman
TI - CL; Radich JP FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia.
SO - Blood 2001 Jun 1;97(11):3589-95
AD - Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA. firstname.lastname@example.org
The prevalence and significance of genetic abnormalities in older patients with acute myeloid leukemia (AML) are unknown. Polymerase chain reactions and single-stranded conformational polymorphism analyses were used to examine 140 elderly AML patients enrolled in the Southwest Oncology Group study 9031 for FLT3, RAS, and TP53 mutations, which were found in 34%, 19%, and 9% of patients, respectively. All but one of the FLT3 (46 of 47) mutations were internal tandem duplications (ITDs) within exons 11 and 12. In the remaining case, a novel internal tandem triplication was found in exon 11. FLT3 ITDs were associated with higher white blood cell counts, higher peripheral blast percentages, normal cytogenetics, and less disease resistance. All RAS mutations (28 of 28) were missense point mutations in codons 12, 13, or 61. RAS mutations were associated with lower peripheral blast and bone marrow blast percentages. Only 2 of 47 patients with FLT3 ITDs also had a RAS mutation, indicating a significant negative association between FLT3 and RAS mutations (P =.0013). Most TP53 mutations (11 of 12) were missense point mutations in exons 5 to 8 and were associated with abnormal cytogenetics, especially abnormalities in both chromosomes 5 and 7. FLT3 and RAS mutations were not associated with inferior clinical outcomes, but TP53 mutations were associated with a worse overall survival (median 1 versus 8 months, P =.0007). These results indicate that mutations in FLT3, RAS, or TP53 are common in older patients with AML and are associated with specific AML phenotypes as defined by laboratory values, cytogenetics, and clinical outcomes. (Blood. 2001;97:3589-3595)
UI - 11861382
AU - Wosikowski K; Mattern K; Schemainda I; Hasmann M; Rattel B; Loser R
TI - WK175, a novel antitumor agent, decreases the intracellular nicotinamide adenine dinucleotide concentration and induces the apoptotic cascade in human leukemia cells.
SO - Cancer Res 2002 Feb 15;62(4):1057-62
AD - Pharmacology Department, Klinge Pharma, 81673 Munich, Germany. email@example.com
We recently developed a class of novel antitumor agents that elicit a potent growth-inhibitory response in many tumor cells cultured in vitro. WK175, a member of this class, was chosen as a model compound that showed strong in vitro efficacy. WK175 interferes with the intracellular steady-state level of NAD(+), resulting in a decreased cellular NAD(+) concentration. We found that WK175 induces apoptotic cell death without any DNA-damaging effect. The apoptotic death signaling pathway initiated by WK175 was examined in detail: mitochondrial membrane potential, cytochrome c release, caspase 3 activation, caspase 3 and poly(ADP-ribose) polymerase cleavage, and the appearance of a sub-G(1) cell cycle population were determined in time course studies in THP-1 (a human monocytic leukemia cell line) cells. We found activation of this cascade after 24 h of treatment with 10 nM WK175. Induction of apoptosis was prevented by bongkrekic acid, Z-Asp-Glu-Val-Asp-fluoromethylketone, and Z-Leu-Glu-His-Asp-fluoromethylketone, inhibitors of the mitochondrial permeability transition and of caspase 3 and 9, respectively, but not by Ac-Tyr-Val-Ala-Asp-CHO, a specific caspase 1 inhibitor, suggesting the involvement of the permeability transition pore, caspase 3, and caspase 9 in the WK175-induced apoptotic cascade. These results imply that decreased NAD(+) concentration initiates the apoptotic cascade, resulting in the antitumor effect of WK175.
UI - 11890991
AU - Tchinda J; Volpert S; Neumann T; Kennerknecht I; Ritter J; Buchner T;
TI - Berdel WE; Horst J Novel der(1)t(1;19) in two patients with myeloid neoplasias.
SO - Cancer Genet Cytogenet 2002 Feb;133(1):61-5
AD - Institut fur Humangenetik, Westfalische Wilhelms-Universitat, Vesaliusweg 12-14, Munster, Germany. firstname.lastname@example.org
Cytogenetic studies can be useful in the clinical management of patients with leukemia. They may also give a clue to leukemogenesis and/or pathogenesis. Numerous disease-specific chromosomal aberrations have been and continue to be identified. Translocation (1;19)(q21 through q23;p13.3) involving the long arm of chromosome 1 and the short arm of chromosome 19 is usually associated with acute lymphoblastic leukemia. We found a new translocation involving one virtually identical breakpoint 19p13 and one distinct 1p13 in two cases of myeloid neoplasms. Studies of bone marrow and peripheral blood specimens specified in one of our patients acute myeloid leukemia and in an other myelodysplastic syndrome. Conventional cytogenetics was supplemented by spectral karyotyping (SKY), microdissection, and fluorescence in situ hybridization. Our first case showed a der(1)t(1;19)(p13;p13.1) as the sole chromosomal change. In addition to this translocation, a pericentric inversion within chromosome 10 and with a cryptic t(10;11) were detected by SKY in the second case. Translocation (1;19)(p13;p13.1) may play a role in the leukemogenesis of myeloid diseases.
UI - 11868094
AU - Tanaka N; Matsumoto T; Miura G; Emoto T; Matsunaga N; Satoh Y; Oka Y
TI - CT findings of leukemic pulmonary infiltration with pathologic correlation.
SO - Eur Radiol 2002 Jan;12(1):166-74
AD - Department of Radiology, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. email@example.com
The aim of this study was to demonstrate the characteristic CT findings of leukemic pulmonary infiltration based on the pathologic findings. The CT findings of 11 leukemic patients with leukemic pulmonary infiltration were compared with those of 22 leukemic patients with other diseases as a control group. Evaluated pulmonary parenchymal CT findings included thickening of bronchovascular bundles and interlobular septa, prominence of peripheral pulmonary arteries, ground-glass opacities, air-space consolidation, and nodules. The CT-pathologic correlations for leukemic infiltration were evaluated in 7 patients. Frequent parenchymal CT findings were thickening of bronchovascular bundles (81.8%), prominence of peripheral pulmonary arteries (81.8%), and non-lobular and non-segmental ground-glass opacities (90.9%). The first two findings were significantly more frequently observed in leukemic infiltration than in the control group, had good interobserver agreement, and corresponded pathologically to leukemic cell infiltration around the pulmonary arteries, bronchi, or bronchioles. Non-lobular and non-segmental ground-glass opacity corresponded to leukemic cell infiltration within alveolar spaces and septa adjacent to the pulmonary arteries or bronchi and also corresponded to hemorrhage, edema, or diffuse alveolar damage. Thickening of bronchovascular bundles and prominence of peripheral pulmonary arteries are CT findings suggestive for leukemic infiltration and correspond to peribronchovascular tumor extension.
UI - 11865595
AU - Cielinska S; Urbaniak-Kujda D; Kapelko-Slowik K; Kuliczkowski K
TI - [The role of costimulatory molecules in immune responses in acute leukemia]
SO - Pol Arch Med Wewn 2001 May;105(5):417-21
AD - Katedra i Klinika Hematologii i Chorob Rozrostowych AM we Wroclawiu.
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