Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fanconi anemia (FA) is an autosomal recessive syndrome with a marked predisposition to malignancies, in particular acute myeloid leukemia and squamous cell carcinoma of the oral cavity. We examined oral squamous cell carcinoma tissue from two FA patients (FA-A and FA-C) by comparative genomic hybridization. Both tumors, which were negative for human papilloma as well as Epstein-Barr viral sequences, showed multiple alterations with a high proportion of whole-arm chromosomal gains and losses. This combination of features as well as the sites involved in chromosomal breakage are very similar to what is typically observed in non-FA oral tumors. These results suggest that the process leading to early occurrence of oral cancer in FA patients follows a similar pathway as in non-FA cancer patients, which would support a caretaker function for FA genes in the protection against oral carcinogenesis. Since FA patients are uniquely hypersensitive to DNA cross-linking agents, while oral cancer in the general population is thought to be environmentally induced, these results also suggest that environmental DNA cross-linkers may be causally involved in oral carcinogenesis.
 ...
PMID:Cytogenetic characteristics of oral squamous cell carcinomas in Fanconi anemia. 1457 14

Fanconi anaemia (FA) is a chromosomal instability disorder associated with a high risk of acute myeloid leukaemia (AML). Previous work has shown that the AML cell line CHRF-288, derived from a sporadic AML-M7 patient, does not express FANCF protein and exhibits a cellular FA phenotype. We show that this phenotype is corrected by a FANCF-expressing plasmid and that the absence of FANCF protein is explained by hypermethylation of the promoter region of the FANCF gene. As FANCF is localized in a hot-spot region for somatic hypermethylation (11p15), FANCF silencing might be an early step in sporadic carcinogenesis, including leukaemogenesis.
 ...
PMID:Bi-allelic silencing of the Fanconi anaemia gene FANCF in acute myeloid leukaemia. 1461 7

Fanconi anemia (FA) is an autosomal recessive syndrome featuring diverse symptoms including progressive bone marrow failure and early occurrence of acute myeloid leukemia. Nine genetic subtypes have been described for FA (A, B, C, D1, D2, E, F, G, and L), all of which have been connected to distinct disease genes, except B. Here we report on 8 unrelated FA patients who were excluded from the known subtypes on the basis of phenotypic correction or genetic data. Four of these cell lines failed to complement each other in somatic cell hybrids and therefore represent a new group, termed FA-I. The remaining cell lines complemented group FA-I but did not complement each other, thus representing a second new group, FA-J. Both FA-I and -J cell lines were capable of forming an FA multiprotein core complex. This complex is required for activation of the FANCD2 protein by mono-ubiquitination, a key downstream event in the FA pathway. In FA-I cells FANCD2 was not mono-ubiquitinated, indicating a defect upstream in the FA pathway, whereas in FA-J cells FANCD2 was mono-ubiquitinated, indicating a downstream defect. Our results suggest that the FA pathway of genome stabilization may be controlled by at least 11 different genes, including FANCI and FANCJ.
 ...
PMID:Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes. 1463 Aug

Fanconi anemia is a chromosomal instability syndrome associated with certain congenital abnormalities, defective hemopoiesis, and an increased risk of developing acute myeloid leukemia and some solid tumors. The diagnosis can be made at birth if congenital abnormalities are present but is often made in childhood when hematologic complications develop. The authors report a case of Fanconi anemia diagnosed in a child with no congenital abnormalities and normal bone marrow who first presented with a cerebellar medulloblastoma. The authors discuss diagnostic and therapeutic implications for such malignancies in Fanconi anemia.
 ...
PMID:Medulloblastoma as a first presentation of fanconi anemia. 1470 15

Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder caused by mutations in one of seven known genes (FANCA,C,D2,E,F,G and BRCA2). Mutations in the FANCA gene are the most prevalent, accounting for two-thirds of FA cases. Affected individuals have greatly increased risks of acute myeloid leukemia (AML). This raises the question as to whether inherited or acquired mutations in FA genes might be involved in the development of sporadic AML. Quantitative fluorescent PCR was used to screen archival DNA from sporadic AML cases for FANCA deletions, which account for 40% of FANCA mutations in FA homozygotes. Four heterozygous deletions were found in 101 samples screened, which is 35-fold higher than the expected population frequency for germline FANCA deletions (P<0.0001). Sequencing FANCA in the AML samples with FANCA deletions did not detect mutations in the second allele and there was no evidence of epigenetic silencing by hypermethylation. However, real-time quantitative PCR analysis in these samples showed reduced expression of FANCA compared to nondeleted AML samples and to controls. These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML.
 ...
PMID:Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia. 1474 3

We have reviewed the world's literature that addresses familial leukemia, lymphoma, and myeloma. We have catalogued the phenotypic abnormalities associated with an increased risk of developing a hematological malignancy. These syndromes, such as Fanconi anemia or familial platelet syndrome, have been well characterized and in many cases the gene responsible for the predisposition has been defined. We have focused, however, on reports of a familial incidence of hematological malignancy in which no prior predisposing syndrome was reported. In this circumstance, so-called pure familial leukemia, lymphoma, or myeloma, the intergenerational incidence of disease occurred in ostensibly healthy persons. These families have been grouped into sets in which (a) anticipation, (b) immune abnormalities, (c) linkage to HLA phenotypes, (d) linkage to chromosome abnormalities, or (e) gene abnormalities have been reported. They have also been grouped by type of leukemia. Purely descriptive reports, not accompanied by some information on pathogenesis, have not been included. They are catalogued in some of the references cited in this paper. Anticipation is a prominent feature of familial leukemia, lymphoma, and myeloma, supporting the concept of germline transmission of a susceptibility gene. Although linkage to an HLA phenotype occurs in some families, no consistent intrafamilial pattern has emerged. Deletion of chromosome 7 is associated with familial acute myelogenous leukemia, but no other recurring localization has been established. Although putative susceptibility genes have been identified in some families, the likelihood is that the mode of inheritance is different in different families and different genes are involved even within a specific Mendelian pattern. Although as yet not reported, the frequency of familial CLL and the intensity of its study indicates that the gene or genes involved in that familial disorder(s) should be identified conclusively soon if sufficient families for study can be assembled through international cooperation.
 ...
PMID:Familial (inherited) leukemia, lymphoma, and myeloma: an overview. 1475 42

Telomeres represent the nucleoprotein tails of chromosomes that get shortened with each cell division. When the telomere length reaches a critical point, cell senescence and death occur. Telomerase is a reverse transcriptase that counteracts telomere loss by adding telomeric sequences. In patients with acquired aplastic anemia, the mean telomere length (TRF) of peripheral blood leukocytes is generally short when compared to normal controls, without it being clear whether a relationship between TRF and disease severity exists. Additionally, increased telomerase activity (TA) is found in the bone marrow mononuclear cell population (MNCs) of aplastic anemia patients, especially in the chronic form of the disease. Fanconi anemia (FA) patients generally demonstrate increased TA and short telomeres in peripheral blood MNCs, a fact attributed to the high turnover of hematopoietic progenitor cells in combination with direct breakages at telomeric sequences. Furthermore, a strong correlation has been shown between TRF and the severity of aplastic anemia, but not with FA evolution towards myelodysplastic syndrome or acute myeloblastic leukemia. In respect of dyskeratosis congenita (DC), a disease of either X-linked or autosomal dominant/recessive inheritance which is characterized by premature ageing of highly regenerative tissues, studies have been carried out in order to elucidate whether the X-linked DC is caused by a defect in ribosomal RNA processing and/or telomere maintenance. Finally, the direct genetic link established between DC pathogenesis and short telomeres may lead to the development of new therapeutic protocols for diseases characterized by short telomere length and subsequent genomic instability.
 ...
PMID:Telomere length variation and telomerase activity expression in patients with congenital and acquired aplastic anemia. 1503 32

Fanconi anemia (FA) is an autosomal recessive condition associated with bone marrow failure (BMF) leading to death or hematopoietic stem cell transplantation, acute myeloid leukemia (AML), and solid tumors (STs). It is unclear which patients are most likely to develop each outcome. From a cohort of 144 North American patients with FA, we calculated individualized risks of each outcome, given the presence or absence of readily diagnosed congenital abnormalities that occur frequently in FA. Abnormal radii and a 5-item congenital abnormality score were significant risk factors for BMF. The cumulative incidence of BMF by age 10 years varied from 18% in the lowest BMF risk group to 83% in the highest. Because of competing risks, patients in the lowest BMF risk group were most likely to live long enough to develop AML or ST, and, conversely, patients in the highest BMF risk group were least likely to live long enough to develop AML or ST. By age 40, the cumulative incidence of ST ranged from 0.6% to 29% in the highest and lowest BMF risk groups, respectively. Abnormal radii are the strongest predictor of early BMF in FA; a congenital abnormality score separates patients with normal radii into distinct prognostic groups.
 ...
PMID:Individualized risks of first adverse events in patients with Fanconi anemia. 1505 44

Despite progress in AML therapy, most patients eventually relapse, even the ones with normal or favorable karyotype. Since survival is poor once relapse occurs, new genetic tools above karyotype at diagnosis are needed to predict leukemia free survival. Recently, Flt3/ITD has been reported as an independent marker for clinical outcome in most studies concerning adult AML patients. To assess the prognostic relevance of activating mutations of Flt3, pretreatment samples of 100 not-M3 AML patients, all of them subjected to an intensive chemotherapy regimen, were analyzed for Flt3/ITD; 25/100 patients had one or more Flt3-ITD. Flt3/ITD patients had higher WBC count (P = 0.005), a lower incidence of a preceding MDS (P = 0.004) and most of them had a normal karyotype. Flt3/ITD had no impact on CR achievement while karyotype remained the most powerful prognostic factor (HR 2.8 95% CI 1.2 6.3). However, post-remission outcome was significantly worsened by the presence of Flt3/ITD. Median RFS of the Flt3/ITD patients was 5 vs. 27 months compared to the patients with wild-type Flt3 (P = 0.0002); moreover, Flt3/ITD patients had a significantly poorer post-remission survival (11 vs. 38 months, P = 0.01). On multivariate analysis, the presence of Flt3-ITD significantly affected relapse free survival and post-remission survival (HR 3.1 and 2.1, respectively). Thus, post-remission outcome highly depends on Flt3 status. Flt3 mutations identify patients at high risk of relapse, who should prospectively receive, according to age, either more aggressive or alternative therapeutic approaches.
 ...
PMID:Internal tandem duplications of Flt3 gene (Flt3/ITD) predicts a poor post-remission outcome in adult patients with acute non-promyelocytic leukemia. 1506 Dec

Fanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder, which is characterized by congenital abnormalities, defective haemopoiesis and a high risk of developing acute myeloid leukaemia and certain solid tumours. It can be caused by mutations in at least eight different genes. Molecular studies have established that a common pathway exists, both between the FA proteins and other proteins involved in DNA damage repair such as NBS1, ATM, BRCA1 and BRCA2. This review summarizes the general clinical and specific haematological features and the current management of FA. Recent molecular advances will also be discussed in the context of the cellular and clinical FA phenotype, with particular emphasis on the haematological aspects of the condition.
 ...
PMID:Fanconi anaemia and leukaemia - clinical and molecular aspects. 1523 38


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