National Cancer Institute®
Last Modified: October 1, 2002
UI - 2386384
AU - Jackson SK; Parton J; Shortland G; Stark JM; Thompson EN
TI - Serum immunoglobulins to endotoxin core glycolipid: acute leukaemia and other cancers.
SO - Arch Dis Child 1990 Jul;65(7):771-3
AD - University of Wales College of Medicine, Heath Park, Cardiff.
Circulating antibody to endotoxin core glycolipid and total serum immunoglobulin concentrations were measured in 86 children with cancer (54 with acute lymphoblastic leukaemia, four with acute myeloid leukaemia, and 28 with various solid tumours). Measurements were made before treatment in the group with acute lymphoblastic leukaemia as well as when patients were both on and off chemotherapy. In the other two groups measurements were made when patients were both on and off treatment. Significant reductions in endotoxin antibody and serum immunoglobulin concentrations were found only in patients with acute lymphoblastic leukaemia. In addition, there was a significant correlation between febrile episodes and the concentration of antibody to core glycolipid in the children with acute lymphoblastic leukaemia. These findings suggest that the use of prophylactic high titre endotoxin antibody may be of benefit to children with life threatening Gram negative infections who are receiving cytotoxic chemotherapy.
UI - 1500128
AU - Choudhry VP; Krishnamurthy L; Arya LS; Desai N; Pati H
TI - Causes of mortality in children with acute lymphocytic leukemia.
SO - Indian Pediatr 1992 Jun;29(6):709-13
AD - Department of Hematology, All India Institute of Medical Sciences, New Delhi.
Fifty five deaths between January, 1982 to September, 1989 in children with acute lymphoblastic leukemia (ALL) were evaluated to determine the cause of mortality. Fifty cases died during remission. Infection alone was responsible for death in 26 of 55 (47.3%) cases while hemorrhage was seen in 7 (12.7%) children. Infection and hemorrhage together were responsible in another 13 cases. Gastrointestinal tract and pulmonary system were the major sites of bleeding. Infections either alone or in combination with other factors were responsible for death in 42 of 55 (76.5%) of children. Septicemia (n = 11), gastrointestinal (n = 15) and pulmonary infections (n = 10) and meningitis in 2 cases were the major sites of infections. Pseudomonas and Klebsiella in 6 cases each accounted for 54.5% of isolates.
UI - 11937268
AU - Zhang Y; Lu J; van den Berghe J; Lee SH
TI - Increased incidence of spontaneous apoptosis in the bone marrow of hyperdiploid childhood acute lymphoblastic leukemia.
SO - Exp Hematol 2002 Apr;30(4):333-9
AD - Department of Pathology, National University Hospital, National University of Singapore, Singapore 119074.
OBJECTIVE: Hyperdiploidy of 51-65 chromosomes is associated with a good prognosis in childhood B-lineage acute lymphoblastic leukemia (ALL). Blasts from childhood ALL patients with a hyperdiploid karyotype have a tendency to apoptosis when cultured on stromal layers in vitro. In this study, we apply a novel method to investigate the relationship between apoptosis and hyperdiploidy in lymphoblasts of childhood ALL. MATERIALS AND METHODS: The DNA content of individual ALL blasts in Feulgen-stained archival bone marrow smears can be determined by static cytometry. TUNEL (TdT-mediated dUTP-biotin nick end labeling) detects the DNA degradation associated with apoptosis. We performed TUNEL in situ sequential to DNA ploidy analysis in archival bone marrow smears from 12 patients with childhood ALL. RESULTS: Five patients were diploid and seven were hyperdiploid (51-65 chromosomes) by conventional cytogenetic analysis. In the five diploid cases, the percentage of TUNEL-positive blasts ranged from 1.0% to 1.3%; in the seven hyperdiploid cases, the percentage of TUNEL-positive blasts ranged from 3.6% to 9.0%. Comparing TUNEL and corresponding Feulgen images, we found that apoptotic blasts were predominantly of high DNA ploidy in both diploid and hyperdiploid cases. The mean DNA value of apoptotic blasts was larger than that of the total blast population in each case. CONCLUSIONS: The results demonstrate an increased incidence of spontaneous apoptosis in situ of hyperdiploid blasts in ALL bone marrow and indicate that this phenomenon is not restricted to in vitro cultures. The findings provide a possible rationale for the good prognosis associated with hyperdiploid childhood ALL.
UI - 11998893
AU - Tsukasaki K
TI - Genetic instability of adult T-cell leukemia/lymphoma by comparative genomic hybridization analysis.
SO - J Clin Immunol 2002 Mar;22(2):57-63
AD - Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan.
Adult T-cell leukemia/lymphoma (ATL) is a distinct clinicopathological entity, i.e., peripheral T-lymphocytic malignancy caused by human T-lymphotropic virus type I (HTLV-1) with diverse clinical features. High frequency of genetic instability (GIN) in both aggressive and indolent ATL was detected by comparative genomic hybridization (CGH). Among GIN, chromosomal instability, i.e., ancuploidy, in indolent ATL was as frequent but less complex and dynamic as compared to those in aggressive ATL. Some of the CGH alterations, including gain of 14q32, appear to be rather ATL specific. Clonal instability of HTLV-1-infected T cells. i.e., emergence of distinct clone, was detected in about one forth of acute crisis from indolent ATL by CGH and Southern blotting for HTLV-1. Taking together with the previous reports of frequent subtle mutations in several tumor suppressor genes in aggressive ATL, GIN in multistep leukemogenesis of ATL is diverse including clonal, chromosomal, and nucleotide levels.
UI - 12163052
AU - Thomas X; Le QH; Danaila C; Lheritier V; Ffrench M
TI - Bone marrow biopsy in adult acute lymphoblastic leukemia: morphological characteristics and contribution to the study of prognostic factors.
SO - Leuk Res 2002 Oct;26(10):909-18
AD - Service d'Hematologie Clinique, Hopital Edouard Herriot, Lyon, France. email@example.com
Bone marrow (BM) sections were examined in 128 untreated adult patients with newly diagnosed acute lymphoblastic leukemia (ALL), seen in our institution over a 19-year period. BM biopsy was performed in order to assess the incidence, degree and prognostic significance of histological data of the disease. BM features studied were reticular fibrosis, total cellularity, residual hematopoiesis, mitotic activity, and blastic infiltration. T-cell lineage ALL were diagnosed in 23% of the cases, while B-cell lineage ALL represented 70% of the cases. There were 7% of non-T-non-B-cell lineage ALL. The percentage of BM leukemic cells was related to cellularity (P=0.02), while it was related to the disappearance of normal cell lines (P<0.0001). BM cellularity was related to the percentage of circulating leukemic cells at diagnosis (P=0.006). Residual hematopoiesis was related to a higher initial granulocyte count (P=0.04) and lower percentage of circulating blasts (P=0.04). The degree of fibrosis was inversely related to that of BM cellularity (P=0.04). All patients, but four, received standard ALL induction chemotherapy according to different successive protocols. In this whole cohort of patients, complete remission (CR) rate was 78%. Median disease-free survival (DFS) and median overall survival (OS) were 13.7 months and 20.2 months, respectively. In univariate analysis, CR rate was positively affected by mitotic activity (P=0.01) and residual hematopoiesis (P=0.008). OS was positively influenced by a higher leukemic cell mitotic activity (P=0.03) and the persistence of more than two residual normal cell lines in BM (P=0.04). Patients presenting with both of those characteristics had better outcome than patients who did not, as well as, in terms of CR (P=0.03), or DFS (P=0.002), or OS (P=0.003). T-cell lineage ALL and L3 ALL did not significantly influence those results. Our findings did not confirm that among marrow features, reticular fibrosis has any prognostic value. A multivariate analysis of both clinical and histological data was performed to test their prognostic relevance. In a model including age, immunophenotype, Philadelphia chromosome status, mitotic index, and level of normal residual hematopoiesis, the only significant predictor of CR achievement were the persistence of normal residual hematopoietic cell lines (P=0.01) and the mitotic activity of leukemic cells (P=0.002). Philadelphia chromosome status (P=0.03) and age (P<0.0001) were of prognostic value, respectively for DFS and OS.We conclude that some characteristics of BM biopsy afford not only descriptive but also prognostic information for predicting the outcome. The persistence of normal residual hematopoiesis and intense leukemic cells mitotic activity were both factors of favorable outcome, while BM fibrosis did not display any prognostic value.
UI - 12360402
AU - Mamane Y; Grandvaux N; Hernandez E; Sharma S; Innocente SA; Lee JM;
TI - Azimi N; Lin R; Hiscott J Repression of IRF-4 target genes in human T cell leukemia virus-1 infection.
SO - Oncogene 2002 Oct 3;21(44):6751-65
AD - Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, and Department of Microbiology and Immunology, McGill University, Montreal, Canada H3T 1E2.
The human T cell leukemia/lymphotropic virus-1 (HTLV-I) is the etiologic agent of adult T cell leukemia (ATL), an aggressive and fatal leukemia of CD4+ T lymphocytes. Interferon regulatory factor-4 (IRF-4) was shown previously to be constitutively expressed in T cells infected with HTLV-1. In this study, we investigated the role of IRF-4 gene regulation in the context of HTLV-1 infection using gene array technology and IRF-4 expressing T cells. Many potential IRF-4 regulated genes were identified, the vast majority of which were repressed by IRF-4 expression. Cyclin B1, a G2-M checkpoint protein identified as an IRF-4 repressed gene in the array, was further characterized in the context of HTLV-1 infection. All HTLV-1 infected cell lines and ATL patient lymphocytes demonstrated a dramatic decrease in cyclin B1 levels; subsequent analysis of the cyclin B1 promoter identified two sites important in IRF-4 binding and repression of cyclin B1 expression. Furthermore, IRF-4-mediated repression of cyclin B1 led to a significant decrease in CDC2 kinase activity in HTLV-1 infected T cells. IRF-4 expression in HTLV-1 infected T cells also downregulated other genes implicated in the mitotic checkpoint as well as genes involved in actin cytoskeletal rearrangement, DNA repair, apoptosis, metastasis and immune recognition. Several of the identified genes are dysregulated in ATL and may provide important mechanistic information concerning pathways critical to the emergence of ATL.
UI - 11924181
AU - el Omri H; Mili-Fathallah A; Amara H; Ben Youssef Y; Garrouche A; Ben
TI - Said M; Ennabli S [Invasive aspergillosis in the leukemic patient]
SO - Rev Mal Respir 2001 Dec;18(6 Pt 1):607-14
AD - Service d'Hematologie Clinique, CHU Farhat Hached, 4000 Sousse, Tunisie.
Invasive pulmonary aspergillosis (IPA) remains a life threatening complication in immuno-compromised and especially in neutropenic patients. We report our experience in the diagnosis and therapeutic management of IPA in 8 patients with acute leukemia. All patients were neutropenic (PNN < 100/mm3, mean duration = 37 days) when IPA was diagnosed. Clinical signs included fever above 39 degrees and cough in all cases, chest pain in 4 cases, hemoptysis in 3 cases, rales in 5 cases. Chest x ray showed one lesion in 4 cases and multiple lesions in 4 cases. The diagnosis of IPA was established by bronchoalveolar lavage (BAL) in 5 cases, tissue biopsy in one case, positive sputum in one case and it was highly probable in one case. Thoracic computed tomographic (CT) scans were preformed after diagnosis confirmation of IPA and showed one or multiple lesions with air crescent signs. Serological tests were positive in 4 cases late in the course of IPA. All patients were treated with i.v. Amphotericin B. Outcome was favorable in 5 cases and three patients died by massive hemoptysis (in two cases) and systemic aspergillosis (in one case). Early diagnosis and appropriate treatment are essential to improve IPA prognosis.
UI - 12194684
AU - Artigas CG; Melo A; Roa JC; Paez E; Vittini C; Arriagada M; Gonzalez L;
TI - Pflaumer E; Roa I [Detection of BCR-ABL gene sequences using RT-PCR in patients with leukemia in the IX region. Chile]
SO - Rev Med Chil 2002 Jun;130(6):623-30
AD - Departamento Medicina Interna, Facultad de Medicina, Universidad de La Frontera, Casilla 54-D, Temuco-Chile. firstname.lastname@example.org
BACKGROUND: The BCR-ABL fusion gene is the molecular expression of the Philadelphia chromosome. This cytogenetic aberration is the most frequent alteration found in leukemias, which is produced by the translocation t(9;22). Two different fusion proteins are produced depending on the break point (210 kD and 190 kD). The detection of this gene has both diagnostic and prognostic importance, associated with poor prognosis in acute lymphoblastic leukemia (ALL). AIM: To detect BCR-ABL gene sequences in patients with leukemia from the IX Region of Chile. MATERIAL AND METHODS: We studied 58 patients: 5 chronic myeloid leukemia (CML), 35 ALL, 15 acute myeloid leukemia (AML) and 3 biphenotypic leukemia. The gene sequences were detected using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: BRC-ABL gene sequences were positive in all patients with CML, 2 of 35 ALL (one child and one adult). The remaining patients were negative. We found p210 and p190 co-expression in 2 CML and 1 ALL. CONCLUSIONS: Our results are in agreement with other reports. The detection of these and other genetic alterations will allow us to have invaluable diagnostic and prognostic information from our patients with leukemia.
UI - 9343323
AU - Soslow RA; Bhargava V; Warnke RA
TI - MIC2, TdT, bcl-2, and CD34 expression in paraffin-embedded high-grade lymphoma/acute lymphoblastic leukemia distinguishes between distinct clinicopathologic entities.
SO - Hum Pathol 1997 Oct;28(10):1158-65
AD - Department of Pathology, New York Hospital-Cornell Medical Center, New York 10021, USA.
We propose that 12E7 (CD99) expression, along with TdT, bcl-2, and CD34 reactivity in lymphoblastic lymphoma (LyL)/acute lymphoblastic leukemia (ALL), distinguishes this group of neoplasms from small noncleaved cell lymphomas (SNCLs) in both pediatric and adult patients, thereby narrowing the differential diagnosis of high-grade non-Hodgkin's lymphomas and acute lymphoblastic leukemias in paraffin sections. 12E7 (CD99) is one of a group of available antibodies that recognizes the product of the mic-2 gene, which was originally identified in ALL. Despite this, most clinicopathological research has focused on the reactivity of 12E7 in a subset of the small round cell tumors of childhood. Although TdT is widely used in the subtyping of blastic leukemias, its use in the distinction of high-grade lymphomas in paraffin sections has been limited. We collected 24 cases of LyL/ALL (13 B-cell and 11 T-cell) and 15 cases of SNCL from 1984 through 1993. We confirmed the diagnoses using morphology and analysis of immunologic data. We performed immunohistochemistry with the 12E7 antibody, TdT, bcl-2, and CD34 on formalin-fixed, paraffin-embedded material. The patients' ages ranged from 4 to 81 years; nine of the study patients were children. Sixteen of the 24 LyL/ALLs stained with 12E7. In contrast, none of the 15 cases of SNCL reacted with this antibody (chi-square P < .0001). A larger percentage of T-cell LyL/ALLs reacted with 12E7 than did B-cell LyL/ALLs (82% v 54%). Sixteen of 20 LyL/ALLs reacted with the anti-TdT antibody, as compared with none of 11 SNCLs (chi-square P < .0001). Six LyL/ALLs were CD34 positive (of 23), and none of the SNCLs were CD34 positive (0 of 12) (chi-square P = .0519). Bcl-2-positive cases were found among both LyL/ ALLs and SNCLs, although they were more prevalent among LyL/ ALLs (92% v 25%; chi-square P < .0001). When one considers the differential diagnosis of a high-grade lymphoma/acute lymphoblastic leukemia, positive reactions with 12E7, TdT, bcl-2, and CD34 support the diagnosis of LyL/ALL over SNCL. Moreover, we present data that suggests that evaluating for TdT in formalin-fixed paraffin-embedded tissue is a more sensitive test than using either 12E7, bcl-2 or CD34 alone.
UI - 12200352
AU - Bhatia S; Sather HN; Heerema NA; Trigg ME; Gaynon PS; Robison LL
TI - Racial and ethnic differences in survival of children with acute lymphoblastic leukemia.
SO - Blood 2002 Sep 15;100(6):1957-64
AD - Children's Oncology Group, City of Hope National Medical Center, PO Box 60012, Arcadia, CA 91006-6012, USA. email@example.com
Black children with acute lymphoblastic leukemia (ALL) have poor outcomes, but limited information is available for children from other racial and ethnic backgrounds, such as Hispanic and Asian. We undertook a retrospective cohort study of children with ALL treated on Children's Cancer Group therapeutic protocols to determine outcomes by racial and ethnic backgrounds of patients treated with contemporary risk-based therapy. In total, 8447 children (white, n = 6703; Hispanic, n = 1071; black, n = 506; and Asian, n = 167) with newly diagnosed ALL between 1983 and 1995 were observed for a median of 6.5 years. Analysis of disease outcome was measured as overall survival (OS) and event-free survival (EFS) and was adjusted for known predictors of outcome including clinical features, disease biology, socioeconomic status, and treatment era (1983-1989 vs 1989-1995). There was a statistically significant difference in survival by ethnicity (P <.001). Five-year EFS rates were: Asian, 75.1% +/- 3.5%; white, 72.8% +/- 0.6%; Hispanic, 65.9% +/- 1.5%; and black, 61.5% +/- 2.2%. Multivariate analysis revealed that when compared with white children, black and Hispanic children had worse outcomes and Asian children had better outcomes after adjusting for known risk factors. The poorer outcomes among black children were most apparent among patients with standard-risk features (relative risk [RR], 2.0; 95% confidence interval [CI], 1.6-2.5), whereas poorer outcomes in Hispanic children (RR, 1.4; 95% CI, 1.2-1.6) were most evident among patients with high-risk features. Asian children had better outcomes than all racial and ethnic groups among high-risk patients, particularly in the recent era (5-year EFS, 90.9% +/- 6.1%). Racial and ethnic differences in OS and EFS persist among children with ALL who receive contemporary risk-based therapy. Future studies should focus on reasons-perhaps compliance or pharmacogenetics-for those differences.
UI - 12357355
AU - Calero Moreno TM; Gustafsson G; Garwicz S; Grander D; Jonmundsson GK;
TI - Frost BM; Makipernaa A; Rasool O; Savolainen ER; Schmiegelow K; Soderhall S; Vettenranta K; Wesenberg F; Einhorn S; Heyman M Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92.
SO - Leukemia 2002 Oct;16(10):2037-45
AD - Research Laboratory of Radiumhemmet, CCK Karolinska Hospital, Stockholm, Sweden.
Inactivation of the Ink4 gene locus locus on 9p comprising the tumour suppressor gene p16ink4a and its neighbours p14ARF and p15ink4b is common in childhood acute lymphoblastic leukaemia (ALL), but the prognostic significance is controversial. DNA from 230 patients was retrospectively analysed by Southern blotting, single strand conformation polymorphism (SSCP) and sequencing techniques. The results were correlated with clinical characteristics and outcome. One hundred and ninety-four fully analysed patients, similarly treated using the Nordic NOPHO-86 or the current NOPHO-92 protocols, were included in the outcome analysis. Deletions approached a minimally deleted region between the p16ink4a and p15ink4b genes, making the p14ARF gene the most commonly deleted coding sequence. Bi-allelic deletion was associated with high white blood cell count (WBC) (P < 0.001), T cell phenotype (P < 0.001) and mediastinal mass (P < 0.001). Patients with Ink4 locus bi-allelic deletions had an inferior pEFS (P < 0.01) and multivariate analysis indicated that bi-allelic deletion of the p16ink4a and the p14ARF genes was an independent prognostic risk factor (P < 0.05). Sub-group analysis revealed a pronounced impact of deletion status for high-risk patients, ie with high WBC. Deletion-status and clinical risk criteria (WBC) could thus be combined to further differentiate risk within the high-risk group. The analysis of the Ink4 locus adds independent prognostic information in childhood ALL treated by Nordic protocols and may help in selection of patients for alternative treatment.
UI - 12357357
AU - Mancini M; Vegna ML; Castoldi GL; Mecucci C; Spirito F; Elia L; Tafuri
TI - A; Annino L; Pane F; Rege-Cambrin G; Gottardi M; Leoni P; Gallo E; Camera A; Luciano L; Specchia G; Torelli G; Sborgia M; Gabbas A; Tedeschi A; Della Starza I; Cascavilla N; Di Raimondo F; Mandelli F; Foa R Partial deletions of long arm of chromosome 6: biologic and clinical implications in adult acute lymphoblastic leukemia.
SO - Leukemia 2002 Oct;16(10):2055-61
AD - Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy.
Within 285 adult acute lymphoblastic leukemias (ALL) included in the multicenter GIMEMA 0496 trial and prospectively studied by conventional cytogenetics, 18 cases (6%) with long arm deletion of chromosome 6 (6q) were identified. These cases were divided into: (i) del(6q) only (n = 6); (ii) del(6q) plus other numerical and/or structural abnormalities (n = 8); (iii) del(6q) and other 'specific' translocations (n = 4). The biologic and clinical features of the patients carrying this anomaly, as well as their outcome, were compared with those of 267 patients without del(6q). A T cell phenotype was more frequently associated with del(6q) cases in general (P = 0.001) and particularly with cases presenting del(6q) as the isolated abnormality (P = 0.0027). No significant difference with respect to multidrug resistance (MDR)/P glycoprotein expression was observed between the two groups of patients (21% vs 28% of MDR-positive cases, respectively). A BCR-ABL fusion transcript was less frequently detected in cases with del(6q) (11%) compared with those without the anomaly (29%). p15 and p16 deletions were identified by Southern blot analysis in 21% of cases with del(6q) and in 26% of cases without del(6q). In this latter group, a T cell phenotype was less frequently associated with p15 and/or p16 deletion than in the group carrying del(6q) (36% vs 100% of cases, P = 0.011). Overall, patients with ALL and del(6q) had a high complete remission (CR) rate (83%); however, they had a lower 18 month event-free survival (31% vs 41%) and a higher relapse rate (70% vs 37%, P = 0.02) compared with patients without del(6q). To date, this is the largest series of adult ALL cases reported with del(6q) homogeneously treated, which have also been prospectively studied for MDR expression and for the detection of known fusion genes. This anomaly, as an isolated change, identifies a subset of cases with hyperleukocytosis (median WBC count 52 x 10(9)/l) and a strict correlation with a T cell phenotype. Overall, del(6q) seems to be associated with an unfavorable clinical outcome, although this finding will need to be confirmed by extended FISH analysis.
UI - 12357365
AU - Cilloni D; Gottardi E; De Micheli D; Serra A; Volpe G; Messa F;
TI - Rege-Cambrin G; Guerrasio A; Divona M; Lo Coco F; Saglio G Quantitative assessment of WT1 expression by real time quantitative PCR may be a useful tool for monitoring minimal residual disease in acute leukemia patients.
SO - Leukemia 2002 Oct;16(10):2115-21
AD - Division of Hematology and Internal Medicine, Dept of Clinical and Biological Sciences of the University of Turin, Italy.
In order to verify if quantitative assessment of the WT1 transcript amount by the real time quantitative PCR (RQ-PCR) can be used as a marker for minimal residual disease detection, the WT1 transcript amount was determined in BM and PB samples of patients with myeloid and lymphoid acute leukemia, in normal controls, in regenerating bone marrow samples and in purified CD34-positive cells from normal subjects. In 10 patients bearing a fusion gene transcript suitable for minimal residual disease quantitative assessment, we performed a simultaneous analysis of the WT1 and of the fusion-gene transcript at sequential time intervals during follow-up. Sequential WT1 analysis was also performed in five AML patients lacking additional molecular markers. The data obtained show that normal and regenerating BM samples and purified CD34-positive cells consistently express minimal amounts of WT1 transcript and that this is extremely low and frequently undetectable in normal PB. By contrast, high levels of WT1 expression are present in the BM and PB samples of all acute leukemia (AL) cases at diagnosis. The WT1 levels during follow-up were found to follow the pattern of the other molecular markers (fusion gene transcripts) used for MRD monitoring and increased WT1expression in the BM and/or PB during follow-up of AL patients was always found to be predictive of an impending hematological relapse.
UI - 12133444
AU - Liu M; Li R; Hayashi Y; Zhu G; Guo S
TI - [Study on abnormal expression of the p73 gene in childhood acute lymphoblastic leukemia]
SO - Zhonghua Xue Ye Xue Za Zhi 2002 May;23(5):239-42
AD - Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
OBJECTIVE: To investigate the relationship between p73 gene and the development and progression of childhood acute lymphoblastic leukemia (ALL). METHODS: The levels of p73 transcripts in 61 ALL cell lines and 53 childhood ALL patients were assayed using reverse transcriptase-polymerase chain reaction (RT-PCR), and their relationship with the clinicopathological characteristics was analyzed. Besides, the methylation status of p73 exon 1 was analysed by restriction-enzyme related PCR, methylation-specific PCR and bisulfite genomic sequencing in the 61 ALL cell lines. RESULTS: Of the 61 ALL cell lines, 42 showed expression of p73 mRNA, with a negative rate of 31.1%, and of the 53 primary childhood ALL samples, 39 showed expression of p73 mRNA, with a negative rate of 26.4%. Loss of p73 expression was significantly associated with the reduced disease free survival and overall survival of the patients. 39.3% (24/61) of the ALL cell lines showed hypermethylation of p73 exon 1, while normal lymphocytes and most cell lines expressed p73 mRNA were not hypermethylated. CONCLUSION: There was a higher negative expression rate of p73 mRNA in childhood ALL. The main mechanism of the loss expression would be the hypermethylation of p73 gene. p73 gene inactivation might play an important role in the pathogenesis of ALL. Examination of p73 mRNA might have clinical significance in predicting prognosis of childhood ALL.
UI - 11940320
AU - Zhao Y; Yu L; Wang Q; Lou F; Pu J
TI - [The relationship between expression of lung resistance-related protein gene or multidrug resistance-associated protein gene and prognosis in newly diagnosed acute leukemia]
SO - Zhonghua Nei Ke Za Zhi 2002 Mar;41(3):183-5
AD - Hematology Department, The General Hospital of PLA. Beijing 100853, China.
OBJECTIVE: To evaluate the relationship between the expression of lung resistance-related protein (lrp) gene or multidrug resistance-associated protein (mrp) gene and prognosis in untreated acute leukemia (AL) patients. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the expression of lrp and mrp gene in 58 newly diagnosed AL patients. RESULTS: The positive rate of lrp and mrp gene expression in newly diagnosed acute lymphocytic leukemia (ALL) group was 15.0% and 40.0% and it was 15.8% and 42.1% in newly diagnosed acute nonlymphocytic leukemia (ANLL) group. In both the ALL and ANLL groups, the difference of the first complete remission rate in lrp negative and in lrp positive patients was not significant (P > 0.05), the same results were found with mrp gene. The difference of the first complete remission rate between lrp(+)/mrp(+) and lrp(-)/mrp(-) patients was significant (P < 0.05). There was no relationship between lrp and mrp gene. CONCLUSION: Neither lrp nor mrp gene as a single indicator to forecast original multidrug resistance is sensitive, but lrp combined with mrp as one indicator will be sensitive.
UI - 11030043
AU - Harrison CJ
TI - The genetics of childhood acute lymphoblastic leukaemia.
SO - Baillieres Best Pract Res Clin Haematol 2000 Sep;13(3):427-39
AD - Department of Haematology, Royal Free and University College Medical School, London, UK.
In childhood acute lymphoblastic leukaemia (ALL) a number of genetic changes have been identified which provide diagnostic and prognostic information with a direct impact on patient management. The most significant abnormalities include the translocation, t(12;21)(p13;q22), giving rise to the ETV6/AML1 gene fusion; BCR/ABL arising from t(9;22)(q34;q11); re-arrangements of the MLL gene; the E2A/PBX1 from the t(1;19)(q23;p13); re-arrangements of MYC with the immunoglobulin genes and re-arrangements of the T cell receptor genes. Chromosomal deletions, particularly those of the short arms of chromosomes 9 and 12 and the long arm of chromosome 6, have been postulated to be the sites of tumour suppressor genes (TSG). Numerical chromosomal abnormalities are of particular importance in relation to prognosis. High hyperdiploidy (50-65 chromosomes) is associated with a good risk, whereas the outlook for patients with near haploidy (23-29 chromosomes) is extremely poor. In view of the introduction of risk-adjusted therapy into the UK childhood ALL treatment trials, an interphase FISH screening programme has been developed to reveal chromosomal abnormalities with prognostic significance in childhood ALL.
UI - 11215050
AU - Chen Y; Zhang H; Yue B; Li H
TI - Study on P16 gene in acute leukemia.
SO - J Tongji Med Univ 2000;20(3):210-1
AD - Institute of Hematology, Xiehe Hospital, Tongji Medical University, Wuhan 430030.
To study the change of suppressing cancer gene P16 in acute leukemia, the P16 antigen expression of leukemia cell surfaces in 61 cases were investigated with ABC assay and gene structural defects in 51 cases of acute leukemia were examined with multiple comparative PCR method. It was found that antigen expression of P16 in leukemia was obviously lower than that innormal subjects (P < 0.001). At the same time, antigen expression in All was lower than that AML (P < 0.05). No significant difference was found between the complete remission (CR) and non-remission (NR) subjects from AML and ALL groups (P > 0.05). THe exon 2 of P16 gene showed homozygous deletion only inn 4 cases out of 30 cases in ALL. No structural defect was revealed in 21 cases of AML. It was suggested that expression defect of P16 gene was a main cause in development and progression of acute leukemia, and structural defect of exon 2 was not a primary molecular event.
UI - 11386084
AU - Sibella-Arguelles C
TI - The proliferation of human T lymphoblastic cells induced by 5-HT1B receptors activation is regulated by 5-HT-moduline.
SO - C R Acad Sci III 2001 Apr;324(4):365-72
AD - Unite de pharmacologie neuro-immuno-endocrinienne, departement de physiopathologie, Institut Pasteur, 28, rue du Dr-Roux, 75724 Paris, France. firstname.lastname@example.org
Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter and immunomodulator, which has been reported to affect the function of cells in the immune system. The purpose of the herein reported experiments was to investigate whether serotonin could regulate the proliferation of a human T lymphoblastic leukemia cell line (CCRF-CEM cells) and to characterize the 5-HT receptor(s) involved in this phenomenon using a pharmacological approach. The herein presented results show that serotonin alone stimulated the proliferation of CCRF-CEM cells and that this effect could be mimicked by two 5-HT1B/1D receptor agonists (L-694,247 and GR 46611). Serotonin- or L-694,247-induced increase in cell proliferation was inhibited by a selective 5-HT1B receptor antagonist, SB-224289. A recently identified endogenous tetrapeptide, 5-HT-moduline (Leu-Ser-Ala-Leu, LSAL), which specifically antagonizes 5-HT1B/1D receptor activity, was also shown to reverse the stimulating action of L-694,247 on T cell proliferation. Taken together, these results establish the existence of a direct serotonergic control of the T cell proliferation mediated through h5-HT1B receptors. In addition, these results are in favour of an immunomodulatory role of 5-HT-moduline.
UI - 12365028
AU - Wen W; Shu XO; Potter JD; Severson RK; Buckley JD; Reaman GH; Robison LL
TI - Parental medication use and risk of childhood acute lymphoblastic leukemia.
SO - Cancer 2002 Oct 15;95(8):1786-94
AD - Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
BACKGROUND: Few studies have examined the risk of childhood acute lymphoblastic leukemia (ALL) associated with parental medication use. As part of a large case-control study conducted by the Children's Cancer Group, we evaluated the association between maternal and paternal medication use and the risk of ALL in offspring. METHODS: Information on selected medication use in the year before and during the index pregnancy was obtained by telephone interview. Participants included 1842 children of 14 years or younger with newly diagnosed and immunophenotypically defined ALL and 1986 individually matched controls. Data were analyzed using logistic regression models and stratified by immunophenotypes of ALL and age at diagnosis of cases. RESULTS: After adjusting for potential confounders and other medication use, we found that maternal use of vitamins (odds ratio [OR] = 0.7, 99% confidence interval [CI]: 0.5-1.0) and iron supplements (OR = 0.8, 99% CI: 0.7-1.0) only during the index pregnancy was associated with a decreased risk of ALL. Parental use of amphetamines or diet pills and mind-altering drugs before and during the index pregnancy was related to an increased risk of childhood ALL, particularly among children where both parents reported using these drugs (OR = 2.8, 99% CI: 0.5-15.6 for amphetamines or diet pills, OR = 1.8, 99% CI: 1.1-3.0 for mind-altering drugs). Stratified analyses showed that maternal use of antihistamines or allergic remedies and parental use of mind-altering drugs were strongly associated with infant ALL, whereas patterns of association between childhood ALL and parental medication use did not influence markedly the immunophenotypic subgroup of ALL. CONCLUSIONS: The findings of this study suggest that certain parental medication use immediately before and during the index pregnancy may influence risk of ALL in offspring. Copyright 2002 American Cancer Society.
UI - 12385062
AU - Besson C; Plumelle Y; Arnulf B; Gonin C; Panelatti G; Bazarbachi A;
TI - Hermine O [Adult T-cell leukemia/lymphoma. Clinical aspects]
SO - Presse Med 2001 Feb 10;30(5):239-42
AD - Service d'Hematologie clinique, Hopital Necker, 149, rue de Sevres, F75743 Paris.
BACKGROUND DATA: Adult T-cell leukemia/lymphoma (ATL) is a malignant proliferation of activated CD4+ T lymphocytes. The disease is almost exclusively found in patients living in retrovirus HTLV-1 endemic areas. VIROLOGY: In ATL, monoclonal HTLV-1 provirus is integrated into atypical lymphocytes, called clover-leaf lymphocytes. The pathogenic mechanism leading to HTLV-1-induced leukemogenesis remains obscure. The disease generally occurs after a long latency period. FOUR CLINICAL SUBTYPES: The diversity of the clinical presentation has led to the classification of ATL into four subtypes: acute or prototype, lymphoma, chronic, and painless. In the acute form of ATL there is a tumor syndrome associated with paraneoplastic hypercalcemia and a high rate of opportunistic infections due to the immunodepression predominated by cellular immunity. CLINICAL COURSE: Prognosis is poor for the acute and lymphomatous forms with a median survival of 6 and 10 months respectively. Infectious episodes are frequent, often caused by Pneumocystis carinii, and require systematic prophylaxis. Screening for anguilulosis and prophylaxis is also necessary.
UI - 7882134
AU - Duro D; Flexor MA; Bernard O; d'Agay MF; Berger R; Larsen CJ
TI - Alterations of the putative tumor suppressor gene p16/MTS1 in human hematological malignancies.
SO - C R Acad Sci III 1994 Oct;317(10):913-9
AD - INSERM U301 et SDI n. 1954 I du CNRS, Institut de Genetique Moleculaire, Paris, France.
The chromosome band 9p21-22 is frequently rearranged or deleted in a variety of tumors including hematological malignancies. This supports the notion of a tumor suppressor gene in this chromosome region. Indeed, the p16/MTS1 gene encoding a cyclin-dependent kinase (CDK) inhibitor has been shown to be frequently deleted and/or inactivated by nonsense mutations in a number of tumors. We have examined 98 DNA samples from blood, bone marrow cells and lymph node biopsies of patients with leukemia (ALL and AML) or lymphoma (follicular lymphoma and T-cell lymphoma), using Southern blot hybridization and a p16/MTS1-specific probe. Molecular abnormalities, mainly homozygous deletions, were found principally in ALL (8 out of 22 patients), much less frequently in AML (2/32) and lymphoma (2/32). While these data argue in favor of a large involvement of p16/MTS1 in ALL, AML and lymphomas appear to be less frequently implicated.
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