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

A 31-yr-old female with congenital hypoplastic anemia (Diamond-Blackfan syndrome) whose long course terminated in acute myelogenous leukemia is described. In contrast to Fanconi anemia, malignant transformation rarely occurs in congenital hypoplastic anemia. This patient's diagnosis of congenital hypoplastic anemia is supported by her clinical course, absence of renal abnormalities, a negative family history for hematologic disorders, normal chromosome studies, failure of her skin fibroblasts to transform in culture with SV-40 virus, macrocytic erythrocyte indices, erythrocyte enzyme studies, and bone marrow findings. Only two other cases of malignancy have been reported in patients with congenital hypoplastic anemia. The development of malignancy in these patients suggests that malignant transformation may be a concern in the long-term progression of congenital hypoplastic anemia.
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PMID:Congenital hypoplastic anemia (Diamond-Blackfan syndrome) terminating in acute myelogenous leukemia. 27 51

A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia. These patients usually have karyotypically abnormal bone marrow clones, but do not exhibit chromosomal translocations involving breakpoints associated with specific oncogenes; leukemia in FA is more likely to be a multi-step process than a single step transformation. The cellular defect in FA results in chromosomal instability, hypersensitivity to DNA damage, and hypermutability for allele-loss mutations. An update of current research to identify the molecular defect in FA is presented. Characterization of the FA genes should further our understanding of the etiology of leukemia.
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PMID:Fanconi anemia and leukemia: tracking the genes. 154 31

Fanconi anemia (FA) is an autosomal recessive disorder characterized clinically by a progressive pancytopenia, diverse congenital abnormalities, and increased predisposition to malignancy. Although a variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, the unique sensitivity of FA cells to the clastogenic effect of DNA cross-linking agents such as diepoxybutane (DEB) can be used to facilitate the diagnosis. We review all cases of FA reported to have leukemia, preleukemia, or a bone marrow (BM) clonal chromosomal abnormality and include for the first time an analysis of these conditions observed in patients in the International Fanconi Anemia Registry (IFAR). The incidence of acute myelogenous leukemia (AML) in FA patients is more than 15,000 times that observed in children in the general population. Cytogenetic studies of FA-associated leukemias disclose a high frequency of monosomy 7 and duplications involving 1q. There were no occurrences of t(8;21), t(15;17), or abnormalities of 11q, which are associated with M2, M3, and M5 leukemias, respectively, but not with preleukemia. Development of leukemia in FA patients was associated with an exceedingly poor prognosis, with a mean age of death of 15 years. We suggest that all FA patients may be considered preleukemic and that this disorder presents a model for study of the etiology of AML.
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PMID:Leukemia and preleukemia in Fanconi anemia patients. A review of the literature and report of the International Fanconi Anemia Registry. 198 36

Fanconi anemia is a rare autosomal recessive disorder in which affected individuals are predisposed to acute myelogenous leukemia and other malignancies. We report the results of a genetic linkage study involving 34 families enrolled in the International Fanconi Anemia Registry. A significant lod score was obtained between D20S20, an anonymous DNA segment from chromosome 20q, and Fanconi anemia (Zmax 3.04, theta max = 0.12). However, six other anonymous DNA segments from chromosome 20q, including D20S19, which is highly polymorphic and tightly linked to D20S20, showed no or only weak evidence for linkage to Fanconi anemia. An admixture test revealed significant evidence for linkage heterogeneity (chi 2 = 6.10, P = 0.01) at the D20S19 locus. Lod scores suggestive of linkage between Fanconi anemia and this locus were obtained with two of the largest kindreds studied (lods = 2.6 and 2.1, at theta = 0.001). Thus, our data support the provisional assignment of a Fanconi anemia gene to chromosome 20q.
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PMID:Fanconi anemia: evidence for linkage heterogeneity on chromosome 20q. 200 84

We report a single center experience of 222 patients (pts) less than 18 years old transplanted from 1973 to 1987. The median age was 11 years (1-18). The donor was a monozygotic twin (9 pts), an HLA-id sibling (193 pts), an HLA-id, parent (9 pts), a mismatched related donor (9 pts) and a matched unrelated donor (1 pt). Ninety-six pts were transplanted for SAA. Conditioning varied with time but the majority (59 pts) received CY 150 mg/kg and 6 Gy TAI. The long term actuarial survival is 66% with a median follow-up of 3 years. The group who received CY 200 mg/kg and MTX had a 33% long term survival (LTS). GVH was the main complication with 40% acute and 37% chronic GVHD. Chronic GVHD tended to improve with time after 2 to 4 years of evolution. Ninety pts were transplanted for leukemia (35 AML, 45 ALL and 11 CGL), 20 pts were in relapse. Pts in CR had a LTS of 40%, in pts in relapse, it was 12%. The main causes of death were: interstitial pneumonitis (30%), relapse (27%), GVH (15%). Thirty-five pts were transplanted for constitutional disease: Fanconi anemia (FA) (26 pts), Dyskeratosis congenita (2 pts), Blackfan-Diamond erythroblastopenia (2 pts), Glanzmann thrombasthenia (1 pt), osteopetrosis (1 pt) and Gaucher's disease (1 pt). In FA, the LTS is 70% with a CY 20 mg/kg, 5 Gy TAI regimen. In all disease categories, we did not find any influence of donor's sex on GVH and survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pediatric bone marrow transplantation for leukemia and aplastic anemia. Report of 222 cases transplanted in a single center. 267 24

Malignant hemopathies and immune deficiencies are the main indications for allogeneic bone marrow transplantation in children. Among the former, the most common condition is acute lymphoblastic leukemia, in which a bone marrow transplant can be performed during the second or first complete remission (CR). Thirty to 50% and 60 to 75% of these grafts, respectively, are successful. The success rate is 50 to 70% among patients with acute myeloblastic leukemia grafted during the first complete remission, and among patients with chronic myeloid leukemia grafted during the chronic phase. Severe medullary aplasia and Fanconi disease are undoubtedly good indications for bone marrow transplantation, which has a 60 to 70% success rate. Severe combined immune deficiencies (SCID) and Wiskott-Aldrich disease are also good indications for HLA-identical bone marrow transplantation, which is successful in 60% of cases. Among the metabolic diseases, good results have been obtained only in Hurler disease and Gaucher disease. Questionable indications include thalassemia, Blackfan-Diamond disease, and chronic granulomatous disease. Results are disappointing in most metabolic diseases, as well as in non-HLA-identical transplantations in diseases other than SCID.
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PMID:[Allogeneic bone marrow grafts in children. Indications and results]. 268 52

A six-year-old girl with Fanconi anemia (FA) developed acute myeloid leukemia (AML) as the first hematologic manifestation of the syndrome. She remains in remission 18 mo after diagnosis although her management is complicated by unusual sensitivity to chemotherapeutic agents. Marrow cells studied prior to initiation of leukemia therapy showed increased chromosome breakage and an abnormal clone in which a number 7 and a number 8 chromosome were replaced by two marker chromosomes. During the present remission her cultured lymphocytes, bone marrow cells, and fibroblasts showed increased "spontaneous" chromosome breakage as well as enhanced sensitivity to the clastogenic effect of the difunctional alkylating agent diepoxybutane (DEB), features characteristic of FA. Eight months into remission 50% of her marrow cells comprised an abnormal clone, which was monosomic for the number 7 chromosome but had both copies of number 8; in addition a variable number of unique marker chromosomes were present in clonal as well as nonclonal cells. This same marrow sample, upon culture, showed an abnormal growth pattern of CFU-GM, absence of detectable CFU-GEMM and BFUe, non-responsiveness of CFU-GM to inhibition by acidic isoferritins, increased bone marrow acidic isoferritin inhibitory activity, and absence of detectable bone marrow cell-derived GM-CSF. The implications of these findings to leukemogenesis in FA are discussed.
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PMID:Acute myeloid leukemia as the first hematologic manifestation of Fanconi anemia. 695 62

Myelodysplastic syndrome (MDS) in childhood is considered to be very rare, but sound epidemiologic data are lacking. We report a population-based study of MDS in Denmark from 1980 to 1991. The medical charts were reviewed of 988 children identified from the Danish National Hospital Discharge Registry with a diagnosis of myeloid leukemia or blood cytopenia. Blood and bone marrow smears from all cases of possible MDS were re-evaluated. The cases were categorized according to the FAB classification, with the exception of chronic myelomonocytic leukemia (CMML) in which more than 5% myeloblasts in the blood was accepted. Juvenile chronic myeloid leukemia (JCML) was included as CMML. MDS was diagnosed in 46 children representing 9% of all hematologic malignancies in children less than 15 years of age. The annual incidence was 4.0/million and did not increase with time. Refractory anemia with excess of blasts and CMML each accounted for one third of the cases. Down syndrome was present in seven children. Other predisposing conditions included Fanconi anemia, neurofibromatosis, constitutional trisomy 8 mosaicism, and familial leukemia. Only one child had therapy-related MDS. The study indicates that the incidence of childhood MDS is higher than generally assumed and approximate to the incidence of acute myeloid leukemia.
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PMID:Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. 765 25

Acute myelogenous leukemia (AML) is the second most common leukemia in children, with approximately 400 new cases occurring annually in the United States. Worldwide, the highest rates of childhood AML occur in Asia and the lowest rates are reported from India and South America. Numerous genetic risk factors for childhood AML have been defined, including Down syndrome, neurofibromatosis, and Fanconi anemia. Research into environmental risk factors has been limited by the rarity of this disease; however, studies of AML in adults have implicated ionizing radiation, solvents, and petroleum products as potential etiologic agents. The largest analytic study of childhood AML found that occupational exposures of either parent to pesticides, paternal exposure to petroleum products, and postnatal exposures to pesticides are increased in children with AML. In addition, maternal use of marijuana during pregnancy was associated with an increased risk of AML, especially the monocytic subtypes. Further study of childhood AML, including occurrence of the disease as a second malignancy, is needed in order to confirm these findings and to increase our understanding of this leukemia.
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PMID:Epidemiology of childhood acute myelogenous leukemia. 774 71

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).
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PMID:Bone marrow transplantation in Iran. 792 Mar 8


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