1/43. Allogeneic bone marrow transplantation in fanconi anemia from turkey: a report of four cases.bone marrow transplantation (BMT) is currently the treatment of choice for patients with fanconi anemia (FA) if a suitable donor is available. Four children with FA underwent allogeneic BMT from HLA-identical siblings during the period from 1995 to 1996. Pretransplant conditioning was cyclophosphamide (Cy) (20 mg/kg) Thoracoabdominal irradiation (TAI) (500 cGy) /- Antithymocyte globulin (ATG) (2 mg/kg/day x 3). Cyclosporin A (CsA) was used as GvHD prophylaxis. The time of neutrophil (ANC>500) and platelet (>50,000) recovery were at 11-14 and 17-25 days, respectively. One patient with a pretransplant history of multiple transfusions experienced graft rejection and died at day 29 with infection and bleeding. Although three patients sustained engraftment one developed donor originated acute lymphoblastic leukemia (ALL) 18 months after BMT and died with CNS hemorrhage and infection at 25 months following 7 months of chemotherapy. None of the patients developed grade 3-4 acute GvHD. Cytotoxicity included grade II mucositis in all and severe gastroenteritis in one patient. During a follow-up period of 10 months and 2 years, two patients are well with normal blood count, recovering immune function and have a Karnofsky score of 90%.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
2/43. Detection of monosomy 7 in bone marrow by fluorescence in situ hybridization. A study of fanconi anemia patients and review of the literature.monosomy 7 is frequently found in the bone marrow of patients with fanconi anemia (FA), marrow myelodysplasia, or acute myelogenous leukemia and is associated with poor prognosis. In our laboratory, cytogenetic analysis of bone marrow from an FA patient found 2 of 30 cells with monosomy 7, but the results of fluorescence in situ hybridization (FISH) indicated that 83 of 207 cells (40%) had monosomy 7. FISH was then used to analyze two earlier samples from the index case, neither of which had monosomy 7 as determined by standard cytogenetics. The FISH analysis determined that the first sample, taken 19 months earlier, had 8 of 200 cells (4%) with monosomy 7 and the second sample. taken 7 months later, contained 43 of 200 cells (21.5%) with monosomy 7. These results indicate a slow evolution toward monosomy 7 in the patient's bone marrow. Standard metaphase chromosome analysis represents only spontaneously dividing cells, leading us to hypothesize that FISH was detecting monosomy 7 in nondividing cells and that it might be useful in the early detection of abnormal clones. To test this hypothesis, FISH was performed on 13 bone marrow samples from nine patients with FA who did not exhibit monosomy 7 by cytogenetic analysis. monosomy 7 was detected in 3.44% of nuclei in FA patients and in 3% of nuclei in normal controls. To date, none of these nine FA patients have developed monosomy 7 or leukemia. They are being monitored by standard cytogenetics and by FISH to determine whether monosomy 7 develops and whether it can be detected by FISH prior to its detection by standard cytogenetics. As standard practice, we have adopted FISH analysis for monosomy 7 in all patients with FA.- - - - - - - - - - ranking = 2keywords = leukemia (Clic here for more details about this article) |
3/43. MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia with the t(11;16)(q23;p13) which developed in an acute lymphoblastic leukemia patient with fanconi anemia.We describe a boy with fanconi anemia (FA) who developed acute lymphoblastic leukemia (ALL) (FAB-LI) followed by acute myeloid leukemia (AML) (FAB-M5) at relapse. The patient was diagnosed with early pre-B-cell ALL without preceding aplastic anemia and was treated with ALL-oriented chemotherapy which included doxorubicin (a total dose of 140 mg/m(2) administered), which is a topoisomerase II inhibitor. Complete remission was obtained, but after 38 weeks AML developed. The karyotype of ALL cells at diagnosis showed 46,XY, and that of AML cells at relapse was 46,XY, t(11;16)(q23;p13). An MLL gene rearrangement and MLL-CBP chimeric mRNA were found in AML, but not in ALL. A diagnosis of FA was confirmed by an increased number of chromosomal breaks and rearrangements in peripheral blood lymphocytes cultured with mitogen in the presence of mitomycin C. We conclude that this FA patient developed ALL followed by a therapy-related t(11;16)-AML resulting in an MLL-CBP fusion. Further examination of such patients would shed light on leukemogenesis in FA patients. Genes chromosomes Cancer 27:264-269, 2000.- - - - - - - - - - ranking = 10keywords = leukemia (Clic here for more details about this article) |
4/43. aggressive periodontitis associated with Fanconi's anemia. A case report.BACKGROUND: Fanconi's anemia is an autosomal recessive disease associated with chromosomal breakage as well as pancytopenia, skin pigmentation, renal hypoplasia, cardiac defects, microcephaly, congenital malformations of the skeleton, hypogonadism, and increased risk of leukemia. The present report describes the periodontal clinical and microbiological status of an 11-year old male having Fanconi's anemia. methods: polymerase chain reaction analysis to detect human cytomegalovirus (HCMV), Epstein-Barr type 1 virus, and herpes simplex virus (HSV) was performed on paper-point samples pooled from either 3 periodontal sites with advanced attachment loss or 3 gingivitis sites with no clinical attachment loss. Anaerobic bacterial culture examination was performed on the pooled periodontitis sample. RESULTS: The patient suffered from pancytopenia, allergy, asthma, hearing impairment, and mental retardation. dentition consisted of 7 primary teeth, 11 erupted permanent teeth, and 14 unerupted permanent teeth. Most erupted teeth showed severe gingival inflammation with some gingival overgrowth and various degrees of periodontal attachment loss. Genomes of HCMV and HSV were detected in the pooled periodontitis sample and HCMV in the pooled gingivitis sample. The periodontitis sample but not the gingivitis sample revealed HCMV mRNA of major capsid protein, suggestive of active viral infection. The periodontitis sample also yielded actinobacillus actinomycetemcomitans (1.1% of total isolates), fusobacterium species (7.9%), campylobacter species (2.2%), peptostreptococcus micros (3.4%), and candida albicans (0.3%). CONCLUSIONS: Oral features of Fanconi's anemia may include increased susceptibility to periodontitis. It is likely that underlying host defense impairment coupled with periodontal infection by HCMV and A. actinomycetemcomitans contribute to the severe type of periodontitis associated with Fanconi's anemia.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
5/43. Two different karyotypes with 1q abnormalities in a patient with fanconi anemia.We report a case of fanconi anemia in which cytogenetic analysis of bone marrow (BM) samples revealed two distinct karyotypes: 46,XY,dup(1)(q21q42), in the first sample and 46,XY,del(1)(q32) in the second, aspirated 7 months later after acute myeloid leukemia (AML) developed. We discuss the cytogenetic clonal fluctuation common in fanconi anemia, with the Fanconi's anemia (FA) reports available in the literature. Interestingly, we have identified that del(1)(q32) has not been reported before in FA.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
6/43. fanconi anemia and primary cataracts: first case.fanconi anemia or pancytopenia is an autosomal recessive condition presenting with a combination of pancytopenia with a mean age of onset of about eight years, a tendency to leukemia, and congenital anomalies. Although ocular abnormalities have been described, cataracts have not been previously reported. We present a patient with proven fanconi anemia and cataracts.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
7/43. Genetic reversion in an acute myelogenous leukemia cell line from a fanconi anemia patient with biallelic mutations in BRCA2.A 2-year old boy was diagnosed with fanconi anemia (FA) and acute myeloid leukemia (AML). A cell line (termed FA-AML1) was established from blast cells obtained after a second relapse after a successful bone marrow transplant. Histochemical and surface marker analysis confirmed that the cells were derived from the myeloid lineage. cytogenetic analysis revealed multiple chromosomal aberrations, including a ring 7. Stable proliferation of the cultured cells was absolutely dependent on the presence of granulocyte macrophage colony-stimulating factor or interleukin 3. This is the first AML cell line successfully established from a FA patient. Remarkably, FA-AML1 cells appeared to lack the characteristic cellular FA phenotype, i.e., a hypersensitivity to growth inhibition and chromosomal breakage by the cross-linking agent mitomycin C. Genomic dna from the patient showed biallelic mutations [8415G>T (K2729N)and 8732C>A (S2835STOP)] in the breast cancer susceptibility gene FANCD1/BRCA2 [N. Howlett et al., science (Wash. DC), 297: 606-609, 2002]. In the AML cells, however, the 8732C>A nonsense mutation was changed into a missense mutation by a secondary alteration, 8731T>G, resulting in 2835E, which restored the open-reading frame of the gene and could explain the reverted phenotype of these cells. Loss of the FA phenotype by genetic correction of a FA gene mutation during AML progression may be a common late event in the pathogenesis of AML in FA patients, which may be treatment related. This finding suggests a novel mechanistic principle of tumor progression based on the genetic correction of an early caretaker gene defect.- - - - - - - - - - ranking = 5keywords = leukemia (Clic here for more details about this article) |
8/43. Pentasomy 21 in leukemia complicating diamond-Blackfan anemia.We present the cytogenetic pattern of a leukemic infant with diamond-Blackfan anemia (DBA). The karyotype was characterized by clonal evolution involving consecutive gains of chromosome 21 up to pentasomy. No chromosomal changes were present in normal lymphocytes. Such a karyotype evolution has been described in some cases of acute leukemia associated with down syndrome, but rarely in non-Down cases.- - - - - - - - - - ranking = 5keywords = leukemia (Clic here for more details about this article) |
9/43. Cytogenetic characteristics of oral squamous cell carcinomas in fanconi anemia.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.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
10/43. medulloblastoma as a first presentation of fanconi anemia.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.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
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