Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon regulatory factor 1 (IRF-1) is a transcriptional activator in the interferon system and acts as a tumor suppressor. The structurally related IRF-2 represses the effects of IRF-1 by competitive binding to the same DNA sequence elements. Changes in the relative balance between IRF-1 and IRF-2 lead to dysregulation of cell growth and may play a role in the development of neoplasias. The loss of functional IRF-1 has been observed in a number of patients with myelodysplastic syndrome (MDS) and leukemia, suggesting a potentially critical role of IRF-1 in leukemogenesis. We studied the expression of both transcription factors in peripheral blood (PB) and bone marrow (BM) cells of children with juvenile myelomonocytic leukemia (JMML) using RT-PCR and Southern blot hybridization. No significant difference between the expression levels of IRF-1 and IRF-2 could be detected in PB and BM of patients with JMML and normal donors. Although our results are preliminary they suggest that neither the tumor suppressor gene IRF-1 nor the oncogene IRF-2 is involved in the pathogenesis of JMML.
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PMID:Expression of interferon regulatory factor 1 and 2 in hematopoietic cells of children with juvenile myelomonocytic leukemia. 1060 88

We describe a 55-year-old Japanese man with acute minimally differentiated myeloid leukemia (M0) with an inversion in the long arm of chromosome 3, i.e., inv(3)(q21q26). Patients with this chromosomal abnormality usually show normal or elevated platelet counts. However, our case had a low platelet count with megakaryocytic dysplasia at diagnosis. Furthermore, the 3q21q26 aberration is generally detected in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome. To the best of our knowledge, it has also been reported in two cases of AML-M0 with 3q21q26 and this is the third case of AML-M0 with 3q21q26. Thus it is suggested that there is some relationship between this type of karyotype abnormality and leukemogenesis and/or thrombopoiesis.
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PMID:Acute minimally differentiated myeloid leukemia (M0) with inv(3)(q21q26). 1060 3

Long-term survivors of aplastic anemia (AA) have a high incidence of clonal disorders, in particular paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndromes (MDS), and acute nonlymphocytic leukemia. To investigate the potential involvement of N-RAS gene mutations in the predisposition to leukemic evolution, a subset of patients at potentially increased risk for clonal disease was selected based on evidence of existing clonal evolution. Nine patients showed a monoclonal pattern of X-chromosome inactivation, 18 demonstrated a PNH clone, and in 3 MDS developed during the course of this study. No mutations were detected during the aplastic phase of disease; 2 of 3 patients with MDS after AA also showed no mutations. However, in 1 patient in whom the disease transformed from AA/PNH to MDS, a mutation of GGT --> GAT at N-RAS codon 13 became detectable, whereas the PNH mutation disappeared. The authors conclude that N-RAS mutations are not an early event preceding transformation of AA or AA/PNH to leukemia. In a subset of patients, RAS mutations may occur at the time of evolution to MDS, but preexisting RAS mutations do not explain the propensity of AA to leukemogenesis. Although PNH is also associated with leukemia, this may arise in the non-PNH cells, indicating that PIG-A gene mutation is not per se oncogenic. (Blood. 2000;95:646-650)
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PMID:N-RAS gene mutation in patients with aplastic anemia and aplastic anemia/ paroxysmal nocturnal hemoglobinuria during evolution to clonal disease. 1062 75

The human t(3;21)(q26;q22) translocation is found as a secondary mutation in some cases of chronic myelogenous leukemia during the blast phase and in therapy-related myelodysplasia and acute myelogenous leukemia. One result of this translocation is a fusion between the AML1, MDS1, and EVI1 genes, which encodes a transcription factor of approximately 200 kDa. The role of the AML1/MDS1/EVI1 (AME) fusion gene in leukemogenesis is largely unknown. In this study, we analyzed the effect of the AME fusion gene in vivo by expressing it in mouse bone marrow cells via retroviral transduction. We found that mice transplanted with AME-transduced bone marrow cells suffered from an acute myelogenous leukemia (AML) 5-13 mo after transplantation. The disease could be readily transferred into secondary recipients with a much shorter latency. Morphological analysis of peripheral blood and bone marrow smears demonstrated the presence of myeloid blast cells and differentiated but immature cells of both myelocytic and monocytic lineages. Cytochemical and flow cytometric analysis confirmed that these mice had a disease similar to the human acute myelomonocytic leukemia. This murine model for AME-induced AML will help dissect the molecular mechanism of AML and the molecular biology of the AML1, MDS1, and EVI1 genes.
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PMID:Human AML1/MDS1/EVI1 fusion protein induces an acute myelogenous leukemia (AML) in mice: a model for human AML. 1067 31

Rearrangements affecting chromosome band 3q21 are observed in a subgroup of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, little is known about the molecular consequences of such aberrations. We therefore established a PAC contig in the 3q21 breakpoint region and identified potential protein coding sequences by exon trapping. One of the exons isolated was from the human GATA-2 gene, which we showed to be transcribed from telomere to centromere. The majority of 3q21 breakpoints are located telomeric to the transcribed portion of this gene in a region that in mice appears to be necessary for proper promoter function. Results of GATA-2 expression analyses in leukemic cell lines as well as primary patient samples are compatible with the hypothesis that 3q21 aberrations contribute to leukemogenesis through deregulation of the hematopoietic transcription factor GATA-2.
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PMID:Transcription factor GATA-2 gene is located near 3q21 breakpoints in myeloid leukemia. 1087 93

A 51-year-old man was admitted for treatment of severe thrombocytopenia in May 1997. A diagnosis of MDS RA (refractory thrombocytopenia; RTC) was made by bone marrow examination, which revealed mild marrow hypoplasia and a reduced number of megakaryocytes accompanied by micromegakaryocytes and hypolobular megakaryocytes. Chromosome analysis demonstrated 46, XY, t(5;7) (q31;q22) in all 20 cells examined. The patient received only supportive therapy including platelet transfusion, until leukocytosis and monocytosis gradually developed in November 1998. In view of a marked increase in the number of monocytes (more than 3,000/microliter), a diagnosis of CMML was made in December 1998. As the leukocytosis progressed, various inflammatory symptoms such as facial erythema and endophthalmitis developed. Administration of interferon alpha (IFN alpha) unexpectedly worsened the leukocytosis and monocytosis, suggesting abnormal responses of these cells to IFN alpha. Detailed molecular analysis of these cells might reveal a novel mechanism of leukemogenesis associated with 5q31.
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PMID:[Progression of refractory thrombocytopenia to chronic myelomonocytic leukemia accompanied by various inflammatory reactions]. 1102 Sep 95

MLF1 is a novel protein identified as the NPM-MLF1 chimeric protein produced by a t(3;5)(q25.1;q34) chromosomal translocation, which is associated with myelodysplastic syndrome (MDS), often prior to acute myeloid leukemia (AML), except for M3. The clinical features of t(3;5)-positive myeloid disorders suggest that this chimeric protein is involved in dysregulation of progenitor cells with the capability to differentiate into multiple lineages. So far, involvement of wild-type MLF1 in hematopoiesis or in leukemogenesis has not been fully investigated. In the present study, 65 patients with AML and 44 patients with MDS were tested for the expression of MLF1 using the quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. A significantly higher level of MLF1 expression (ratio of MLF1/beta-actin mRNA >0.4) was readily detected in seven of 65 patients with de novo AML, three of 12 with post-MDS AML and seven of 44 with MDS, but not in any patients with ALL (n = 18). According to the FAB classification, high levels of MLF1 were found in patients with relatively immature subtypes of AML (M1, M2, M6 and M7) and high risk MDS (RAEB and RAEB-T). These findings indicate that the pattern of MLF1 expression is identical to the clinical morphology appearing in the t(3;5)-positive myeloid disorders and is correlated to the MDS-associated AML and transformation phase of MDS in t(3;5)-negative myeloid disorders. A CD34+ population of normal bone marrow cells preferentially expressed MLF1 with obviously decreasing levels of expression during maturation. Therefore, MLF1 normally functions in multi-potent progenitor cells and its dysregulation may take part in leukemogenesis from MDS.
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PMID:Elevated MLF1 expression correlates with malignant progression from myelodysplastic syndrome. 1102 51

We report 2 paroxysmal nocturnal hemoglobinuria (PNH) patients who were initially diagnosed with aplastic anemia and sequentially developed PNH, myelodysplastic syndromes (MDS), and leukemia. Flow cytometry and cytogenetic analysis showed the initial appearance and expansion of PNH clones, gradual replacement of PNH clones by MDS clones with monosomy 7, and then expansion of MDS clones or their subclones with additional chromosomal abnormalities. In relation to these developments, expression increased of the Wilms' tumor gene WT1, a marker for leukemic progression. These patients not only shared bone marrow failure but also might have harbored a hematopoietic environment favorable for the emergence of abnormal clones leading to leukemogenesis.
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PMID:Two cases showing clonal progression with full evolution from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome to myelodysplastic syndromes and leukemia. 1103 70

There is increasing evidence that the acute myeloid leukemia 1 (AML-1) gene plays a versatile role in hematopoiesis, and its inactivation has been described in various hematopoetic disorders, e.g., leukemia or familial thrombocytopenia. AML-1 can be affected by various mechanisms, such as chromosomal translocations or point mutations. On the other hand, the specific underlying molecular lesions in myelodysplastic syndromes (MDS) or leukemias with aberrations of chromosomes 5q or 7, respectively, are largely unknown. Despite extraordinary scientific effort no specific genes on chromosome 5q or 7, which act as tumor suppressors, have definitely been identified. Therefore, it has recently been speculated that the AML-1 gene, even if distantly located on chromosome 21q22, may be involved in leukemogenesis in patients with aberrations at chromosome 5q or monosomy 7 [2]. Therefore, we sequenced all exons of the AML-1 gene in 15 patients with MDS/AML and deleted chromosome 5q or 7q, respectively. None of the patients analyzed had any AML-1 mutation.
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PMID:Absence of point mutations within the AML-1 gene in patients with MDS/AML and loss of chromosome 5q or 7. 1126 27

Therapy-related MDS and AML are complications of intensive chemotherapy regimens. Traditionally, patients exposed to topoisomerase II inhibitors are reported to develop secondary AML with abnormalities of chromosome 11q23. We evaluated the long-term hematologic toxicity of topoisomerase II-intensive high-dose mitoxantrone-based chemotherapy in 163 newly diagnosed acute leukemia patients treated over an 8 year period. Nine (5.5%) patients developed new cytogenetic abnormalities. Four patients developed MDS with progression to AML, three patients developed new abnormalities at the time of relapse, and three patients (including one of the former patients) had changes that were not associated with hematologic disease. The abnormalities most frequently involved chromosomes 7q, 20q, 1q, and 13q. Despite the use of topoisomerase II-intensive treatment, no patient developed an abnormality involving chromosome 11q23. Spontaneous resolution of some changes and prolonged persistence of others in the absence of hematologic disease indicates that some cytogenetic changes are not sufficient to promote leukemogenesis.
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PMID:Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy. 1141 84


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