Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Wilms' tumor gene, WT1, is believed to play a role in hematopoiesis as it is expressed in the spleen and in immature leukemias in addition to the developing genitourinary system. WT1 is down-regulated in differentiated leukemia cells both in vivo and in vitro and is up-regulated in fetal spleen and immature leukemia cells. The modulation of WT1 expression was examined in many cell types, and a hematopoietic-specific enhancer element has been identified. Here we describe the transcriptional response of this enhancer to hematopoietic-specific transcription factors. We found co-expression of WT1 and GATA-1 mRNA in K562 cells and in mouse spleen, suggesting potential interactions between these two transcription factors. We find that the activity of the 3' WT1 enhancer is positively correlated with the expression of GATA-1. Gel shift competition experiments and transactivation studies revealed that this functional activity is mediated via binding at a GATA-binding site in the WT1 enhancer. The transactivation of the WT1 enhancer by GATA-1 implies that GATA-1 plays a role in the regulation of WT1 during hematopoiesis.
 ...
PMID:GATA-1 transactivates the WT1 hematopoietic specific enhancer. 789 Jul 25

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
 ...
PMID:WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. 794 79

Leukemias and lymphomas occurring in a series of families with Wilms' tumor (WT) are described. One surviving case developed a large cell anaplastic Ki-1 lymphoma at age 20 years, and 23 second- and higher degree relatives were affected. In two instances leukemia/lymphoma occurred in the context of Li-Fraumeni syndrome (LFS) and two other families showed striking clusters of unusual and early-onset malignancies. In several cases, children had genitourinary abnormalities of the type associated with the WT1 gene on chromosome 11p13. Some of these families may provide important subjects for study of WT genes in hematologic disease and lymphomas and for investigation of interaction between different tumor-suppressor genes, e.g., WT1 and other candidate WT genes, and p53.
 ...
PMID:Leukemia, lymphoma, and related disorders in families of children diagnosed with Wilms' tumor. 795 23

The aim of the present study was to investigate loss of heterozygosity (LOH) or microsatellite instability in chronic myeloid leukaemia (CML) blast crisis at genomic locations which are known or postulated to harbour tumour suppressor genes. We studied 48 patients in blast crisis of myeloid (n = 31), lymphoid (n = 15), megakaryocytic (n = 1), or mixed lineage (n = 1) phenotype by comparing constitutional DNA extracted from buccal epithelial cells or chronic phase leucocytes with DNA obtained from blast crisis leucocytes. Twelve variable number tandem repeat loci from six different chromosomes were amplified by polymerase chain reaction using labelled primers, and fractionated on polyacrylamide gels. After autoradiography, length as well as intensity of the amplified products were compared between constitutional and blast crisis samples. LOH was scored as complete, partial or none in informative patients. Complete LOH was found in one patient at 8p22 and another at 13q14; partial LOH was detected in three patients at 11p13 and/or 11p15. No LOH was found at 6q27, 8p21, 18q21, 22q11-12 and 22q13 in any patient. Furthermore, no consistent difference in allelic length was observed in 517 paired amplifications indicating no microsatellite instability. We conclude that the Rb gene at 13q14, the Wilms tumour gene at 11p13, the DCC gene at 18q21, the neurofibromatosis 2 gene at 22q11-13 and uncloned tumour suppressor genes at 6q27, 8p21-22 and 11p15, as well as genes responsible for microsatellite instability, are unlikely to be involved in the progression of CML to blast crisis in the majority of patients.
Leukemia 1994 Nov
PMID:No evidence for microsatellite instability or consistent loss of heterozygosity at selected loci in chronic myeloid leukaemia blast crisis. 796 38

We reviewed all cytologic specimens of pleural, peritoneal and pericardial fluids examined in our laboratory from patients aged 0-17 years during a 12-year period. A total of 103 specimens were studied: 45 pleural, 54 peritoneal and 4 pericardial. Twenty-two of the 103 specimens were peritoneal washes. Eleven of the 81 (14%) serous effusion specimens contained tumor cells: 8 lymphomas, 1 leukemia, 1 abdominal desmoplastic small round cell tumor and 1 Wilms' tumor. Two false-positive diagnoses were made in patients presenting with ascites with an unknown case. Both cases were complicated by the presence of atypical mononuclear cells and illustrate a potential pitfall in the evaluation of pediatric serous effusions. We conclude: (1) Almost all pediatric effusions are benign. (2) Malignant pediatric effusions are usually caused by neoplasms of the small cell type, mostly lymphoreticular. (3) The major diagnostic difficulty in interpreting pediatric effusion cytology is in distinguishing neoplasms of the small cell type from mononuclear inflammatory cells. (4) The usefulness of peritoneal washings in pediatric patients is similar to that in adults.
 ...
PMID:Cytology of fluids from pleural, peritoneal and pericardial cavities in children. A comprehensive survey. 814 12

Patients with specific disorders in sexual differentiation have an increased risk for development of malignancies. The most frequent malignant tumors to be expected especially in childhood are gonadoblastoma (carcinoma-in-situ) by children with pure gonadal dysgenesis (Swyer-syndrome) with a calculated risk of approximately 30%. In this disorder the so called streak gonads have an age related, increased risk for development of malignancies. Furthermore, malignant tumors may be expected in children with mixed gonadal dysgenesis (in 10-20%), pure hermaphroditism (in the testes significantly higher than in the ovaries) and with androgen insensitivity syndrome. Risk values for the last are reported in the literature very differently. Rare disorders in this context are virilizing tumors of the adrenal cortex, the DRASH-syndrome (nephropathy, most male pseudohermaphroditism, Wilms-tumor) and similar disorders. Practical prophylactic and therapeutic procedures of the separate disorders respectively were discussed. We report about a child with androgen resistance syndrome and acute leukaemia. This would be to our knowledge the first description of such an unusual association of these two distinct disorders.
 ...
PMID:[Intersexuality and malignancy. Case report of an unreported association between a malignant disease in a child with androgen resistance syndrome in comparison with the most frequently expected malignant tumors in children with intersexuality]. 815 7

As the cure rate for childhood malignancies increases, the number of patients at risk for development of second malignancies also increases. Due to the potentially long remaining life span, long-term follow-up is difficult and patients are often at risk after presumptive cures. Some authors believe that cure rates for second malignancies are similar to cure rates for primary malignancies. We reviewed the records of 162 patients seen at our institution who had developed a second malignancy after treatment for childhood cancer. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment (including radiotherapy with dosage when available, and chemotherapy) plus outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3 years. The most common primary malignancy was Hodgkin's disease (33) followed by soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average interval between diagnosis of the first and second malignancy was 10.8 years. These second tumors carried a high mortality. Only 56 patients have no evidence of disease. Five patients are known to be alive with disease and 92 patients have expired due to their second malignancy. Disease status in 8 patients is unknown. The most common second malignancy was osteosarcoma (35) followed by soft tissue sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and others (27).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Forty-year experience with second malignancies after treatment of childhood cancer: analysis of outcome following the development of the second malignancy. 826 99

Autologous bone marrow transplantation is used for children with cancers which are only partially responsive to bone marrow toxic doses of cancer chemotherapy and irradiation. The use of megatherapy and autologous bone marrow transplantation instead of conventional doses for children has yielded substantial benefits in B-cell lymphoma, relapse of leukaemia, disseminated neuroblastoma and germ cell tumors. In the case of Wilms' tumor, rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma with a partial initial response or a relapse, autologous bone marrow transplantation has been used to a limited extent. Based on the best results from conventional therapy and autologous bone marrow transplantation, respectively, the present need for autologous bone marrow transplantation in Denmark is estimated to be 24 transplantations a year.
 ...
PMID:[Autologous bone marrow transplantation in children]. 831 84

Wilms' tumor (WT) is a pediatric malignancy that occurs in embryonic kidney. Recently, a putative Wilms' tumor gene (WT1), located on chromosome 11p13, was isolated and characterized. We found constitutive expression of WT1 mRNA in eight out of 22 hematopoietic cell lines and seven out of 26 clinical samples which were derived from patients with various types of hematologic malignancies. WT1 mRNA was detected in four out of six myeloid cell lines, four out of 10 cases of acute myelocytic leukemia, three out of 15 lymphoid cell lines, one out of nine cases of lymphoid malignancies, and one out of six cases of chronic myelocytic leukemia in accelerated phase and blast crisis. One unclassified hematopoietic cell line and a case of myelodysplastic syndrome also expressed WT1 mRNA. No mutations were detectable in the cell lines by Southern blot analysis and a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis in the four zinc finger domains of the WT1 gene. These results suggest that WT1 gene is expressed in several types of immature lymphoid or myeloid leukemia cells possibly without alterations of the WT1 gene.
Leukemia 1993 Jul
PMID:Expression of the candidate Wilm's tumor gene, WT1, in human leukemia cells. 832 Oct 47

The duration of symptoms before diagnosis (lag time) was defined for 184 of 236 children diagnosed as having a malignancy at the Royal Hospital for Sick Children, Edinburgh for the time period January 1982 until December 1990. The natural logarithm of the lag time was correlated with age, gender, diagnostic group, white cell count in acute leukaemia, clinical stage of disease in solid tumours, and event free survival. Age was significantly associated with lag time, older children presenting later. In the diagnostic groups, mean lag time ranged from 2.8 weeks in nephroblastoma to 13.3 weeks for brain tumours. Diagnostic group was predictive for lag time after adjustment for age, with for example, a significantly longer lag time for those with brain tumours. However lag time was not predictive of event free survival and it is likely that lag time has other major determinants. When compared with previous studies, there also appears to be a regional variation in lag time for diagnostic groups. It seems likely that this is a reflection of geographical difference in the structure of health systems and is therefore yet another important determinant.
 ...
PMID:Determinants of symptom interval in childhood cancer. 833 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>