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

Children with neurofibromatosis type 1 (NF1) are at increased risk of developing malignant myeloid disorders, particularly juvenile chronic myelogenous leukemia/juvenile myelomonocytic leukemia (JCML/JMML). We investigated bone marrows from 11 such patients (8 boys and 3 girls) and detected allelic losses at the NF1 locus in 4 of them and probable losses in 2 others. To determine which hematopoietic cell lineages were derived from the abnormal clones, Epstein-Barr virus (EBV)-transformed cell lines and CD34+ cells were analyzed from 3 children with JCML with allelic losses in unfractionated marrow. CD34 cells from these 3 patients lacked the normal NF1 allele, whereas EBV cell lines retained it. Erythroblasts plucked from the burst-forming unit-erythroid colonies of one of these children lacked the normal NF1 allele. We also studied a 10-month-old boy with NF1 who developed an unusual myeloproliferative syndrome. His bone marrow and EBV cell line both showed loss of the normal NF1 allele. In our series and in the literature, male sex and maternal transmission of NF1 were associated with the highest risk of myeloid leukemia. These data (1) provide strong genetic evidence that NF1 functions as a tumor-suppressor in early myelopoiesis, (2) confirm the clonal nature of JCML/JMML, (3) suggest that the elevation in fetal hemoglobin seen in JCML/JMML is a result of primary involvement of erythroid progenitors in the malignant clone, (4) show consistent loss of NF1 in the CD34 cells of affected children and show that the malignant clone may also give rise to pre-B cells in some cases, and (5) implicate epigenetic factors in the development of leukemia in children with NF1.
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PMID:Patterns of hematopoietic lineage involvement in children with neurofibromatosis type 1 and malignant myeloid disorders. 894 68

Repetitive structure of enhancer elements in the long terminal repeat (LTR) has been identified in feline leukemia viruses (FeLVs) integrated in lymphoid tumor cells in cats. In this study, promoter activities of the FeLV LTRs were measured in lymphoid and non-lymphoid cell lines in transient expression assays using plasmids containing the viral LTRs linked to the chloramphenicol acetyltransferase (CAT) gene. Promoter activity of the LTR with 3 enhancer repeats (pFTLTR) was significantly higher than that of the LTR with 1 enhancer (Glasgow-1 LTR) in feline (FT-1) and human (Jurkat) T-lymphoblastoid cell lines. Promoter activity of the pFTLTR was also significantly higher than that of its mutant (pFTLTR1E) in which 2 of the 3 enhancers were deleted in FT-1 and Jurkat cells. Both of these differences were not observed in a feline fibroblastic cell line (CrFK). Moreover, mutations affecting the consensus motifs for LVb, SV40, NF-1, GRE and FLV-1 resulted in decreased basal activity of the FeLV LTR (pFTLTR1E) in FT-1, Jurkat and CRFK cells. The decrease of the promoter activity was especially remarkable in FT-1 cells. The present study revealed the strong promoter activity of the FeLV LTR with 3 enhancer repeats and its modular enhancer elements positively regulating the transcription in a relatively tissue-specific manner.
Leukemia 1997 Apr
PMID:Regulation of gene expression directed by the long terminal repeats of feline leukemia viruses. 920 39

Juvenile chronic myelogenous leukaemia (JCML) is a rare haematological malignancy of myelomonocytic lineage that affects patients less than 4 years of age and is known as an entity different from adult-type chronic myelogenous leukaemia. In JCML, skin manifestations are relatively common but most of them have been reported as a non-specific eruption, which histologically may show changes resembling neurofibromatosis or xanthogranuloma. We present a 2-year-old boy with JCML who developed a recurrent annular erythema in which leukaemic infiltrates were confirmed histologically, even though his bone marrow examination suggested that be remained in haematological remission.
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PMID:Recurrent annular erythema in juvenile chronic myelogenous leukaemia. 974 74

The enhancer sequences in the Moloney murine leukemia virus (M-MuLV) long terminal repeat (LTR) are of considerable interest since they are crucial for virus replication and the ability of the virus to induce T lymphomas. While extensive studies have identified numerous nuclear factors that can potentially bind to M-MuLV enhancer DNA in vitro, it has not been made clear which of these factors are bound in vivo. To address this problem, we carried out in vivo footprinting of the M-MuLV enhancer in infected cells by in vivo treatment with dimethyl sulfate (DMS) followed by visualization through ligation-mediated PCR (LMPCR) and gel electrophoresis. In vivo DMS-LMPCR footprinting of the upstream LTR revealed evidence for factor binding at several previously characterized motifs. In particular, protection of guanines in the central LVb/Ets and Core sites within the 75-bp repeats was detected in infected NIH 3T3 fibroblasts, Ti-6 lymphoid cells, and thymic tumor cells. In contrast, factor binding at the NF-1 sites was found in infected fibroblasts but not in T-lymphoid cells. These results are consistent with the results of previous experiments indicating the importance of the LVb/Ets and Core sequences for many retroviruses and the biological importance especially of the NF-1 sites in fibroblasts and T-lymphoid cells. No evidence for factor binding to the glucocorticoid responsive element and LVa sites was found. Additional sites of protein binding included a region in the GC-rich sequences downstream of the 75-bp repeats (only in fibroblasts), a hypersensitive guanine on the minus strand in the LVc site (only in T-lymphoid cells), and a region upstream of the 75-bp repeats. These experiments provide concrete evidence for the differential in vivo binding of nuclear factors to the M-MuLV enhancers in different cell types.
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PMID:In vivo footprinting of the enhancer sequences in the upstream long terminal repeat of Moloney murine leukemia virus: differential binding of nuclear factors in different cell types. 976 41

The triple association of leukemia, xanthomatous skin lesions, and neurofibromatosis 1 (NF) was first described by Royer et al. in 1958. Most of the leukemias were of the juvenile chronic myelogenous type (JCML). We describe a 7-year-old male child with xanthoma, neurofibromatosis 1, and juvenile chronic myelogenous leukemia. His mother also had NF1. We suggest that the presence of xanthomas and NF1 in a young child should raise awareness of the possible development of JCML, especially in patients with a family history of NF1.
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PMID:Juvenile chronic myelogenous leukemia, neurofibromatosis 1, and xanthoma. 1006 10

The FAB group has defined myelodysplasia in adults but direct application of this categorization to children has been controversial. Consequently, to outline the natural history of the disease better we have retrospectively analysed case reports and series published in English between 1982 and 1996. This study also included children with juvenile chronic myelomonocytic leukaemia (JCML) and monosomy 7 (Mo7). 340 patients were described in 27 publications. The mean presentation age was 5.91 (SD 5.04) years, and 34.9% were female. Constitutional alterations were described in 68 (20%) where refractory anemia (RA) and RA with excess of blasts (RAEB) predominated and were associated with a significantly longer survival. Among all patients progression to higher forms of MDS was noted in 61 (18%). Cytogenetic anomalies were detected in 59% of 227 children, and in 67 it was to Mo7. Amid those with Mo7, the clinical and laboratory characteristics as well as survival, closely followed their FAB type. Of the treatment options described, survival was significantly higher in those who underwent bone marrow transplant (BMT) (46.9%; P = 0.00021). Among children with JMML (CMML/JCML) not receiving a BMT, time to death was shortest in those best described as JCML (absence of constitutional and karyotypic derangement, thrombocytopenia and elevated Hb F). We conclude that children with constitutional abnormalities survive longer, Mo7 disorders are clinically and morphologically heterogeneous and should not be grouped into a single entity and that CMML and JCML may have biological differences. Finally, BMT remains the treatment of choice for those with primary MDS, as intensive chemotherapy is no better than supportive measures.
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PMID:Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management. 1070 66

Juvenile xanthogranuloma (JXG) is a rare and usually benign disease occurring in early childhood. It causes skin and deep seated lesions, notably in the eye. We report a case of JXG in the iris of a 9-month-old infant. Examination under general anesthesia revealed megalocornea, iris xanthogranuloma occupying the entire anterior chamber and high intraocular pressure. Skin lesions on the left lid and on the back were also found. Ocular hypertension resisted medical and surgical treatment. Cyclodestruction was necessary. The incidence of JXG is low (0.4%). The iris is the most frequently affected ocular tissue. Early diagnosis is necessary to avoid complications. Moreover, JXG can be associated in rare cases with neurofibromatosis or leukemia which must be systematically searched for.
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PMID:[Juvenile xanthogranuloma with intraocular involvement. A case report]. 1103 5

Recent progress in the understanding of signal transduction and gene regulation in hematopoietic cells has shown that many intracellular signalling pathways are modulated by low molecular weight guanine nucleotide (GTP)-binding proteins (LMWGs). LMWGs act as molecular switches for regulating a wide range of signal-transduction pathways in virtually all cells. In hematopoietic cells, LMWGs have been shown to participate in essential functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemoattractant-induced signalling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, intracellular vesicle transport and secretion. In human leukemias, myelodysplastic syndromes and myeloproliferative disorders, Ras activation occurs by point mutations, overexpression or by alteration of NF-1 Ras-GTPase activating protein (GAP). These are postinitiation events in leukemia but may modulate growth-factor-dependent and independent leukemic growth. Two animal models of mutated N-ras expression resulting in myelodysplastic and myeloproliferative features are discussed. The role of Ras in organ development is discussed in the context of transgenic knockout mice. More LMWG functions will certainly be identified as we gain a better understanding of regulatory pathways modulating myeloid signal transduction. This review will summarize our current understanding of this rapidly advancing area of research.
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PMID:The role of ras and other low molecular weight guanine nucleotide (GTP)-binding proteins during hematopoietic cell differentiation. 1121 20

The leukemogenic potential of alkylating agents has been known for many years and almost all alkylating agents in clinical use have been shown to increase the risk of leukemia. With these drugs the risk of leukemia appears to increase with increasing patient age, as does the risk of de novo myeloid leukemia in the population. Susceptibility to alkylating agent-associated leukemia is influenced by the genetic constitution of the patient, and by the nature of the exposure. To illustrate the importance of these factors in etiology of leukemia, this paper discusses the contribution of disorders such as Fanconi anemia and neurofibromatosis to susceptibility to alkylating agent-associated leukemia. This paper also discusses the contribution of alkylating agents and other therapeutic exposures in the etiology of leukemias occurring after autologous bone marrow transplant.
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PMID:Therapy-related leukemia associated with alkylating agents. 1134 Jun 8

We report a retrospective analysis of children with myelodysplastic syndrome (MDS) diagnosed between 1990 and 1997 in Japan. In total, 189 patients were enrolled: 122 cases of primary MDS (26 RA, 18 RAEB, 25 RAEBt, 53 CMML/JMML), 24 cases with constitutional predisposition to MDS, and 43 cases of therapy-related MDS (t-MDS). The frequency of pediatric MDS was estimated to be 7.7% of all leukemias. Cytogenetic abnormalities were observed in 41% of primary MDS and 90% of t-MDS cases. The 4-year survival rate, estimated by Kaplan-Meier analysis, for primary RA was 78.9%, while other types of MDS and JMML had rates lower than 40%, and t-MDS showed an even more unfavorable prognosis. In primary MDS, the survival rate of patients with cytogenetic abnormalities was significantly lower. Among prognostic variables by IPSS, only the cytogenetic pattern was useful for predicting outcome in childhood MDS. There was no apparent advantage to chemotherapy for RA, and the survival rate in patients with primary RA, JMML, or t-MDS receiving stem cell transplantation was significantly higher. More precise designs of our diagnostic and classification systems, as well as therapeutic trials in large-scale prospective studies, are necessary for further improvements in MDS outcome.
Leukemia 2001 Nov
PMID:Myelodysplastic syndrome in childhood: a retrospective study of 189 patients in Japan. 1168 12


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