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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelodysplastic syndromes originate from a pluripotent stem cell. This view, previously suggested by G-6-PD and cytogenetic investigations, has been established unequivocally by X-chromosome inactivation analysis based on DNA polymorphisms and by studies of mutated oncogenes. Two genomic alterations associated with MDS have been analyzed in more detail. Activation of the RAS oncogenes, preferentially N-RAS, is demonstrated in approximately 35% of MDS patients. Mutations in the FMS gene, encoding the CSF-1 receptor, are found in 16% of cases. Interestingly, RAS and FMS mutations are predominantly observed in disorders of myelomonoctic differentiation, i.e., the CMML subtype in MDS and the AML FAB type M4. Moreover, homozygous deletion of the FMS gene may be an important event in the genesis of the MDS variant 5q- syndrome. Preliminary data indicate that defects in tumor-suppressor genes, namely p53, may also contribute to the development of MDS. Different lines of evidence suggest that clinical preleukemia is preceded by a phase in which genetic alterations accumulate without any hematologic change. Cases in point are the detection of RAS and FMS mutations in healthy individuals who had been treated in the past with cytotoxic therapy for lymphoma, the frequent observation of clonal remission in AML patients, or the identification of oncogene mutations in healthy individuals without even a history of malignancy or chemotherapy. Possibly, either germline mutations of oncogenes or tumor-suppressor genes and the process of genomic imprinting may constitute additional factors that predispose hematopoietic stem cells to malignant transformation. Limited as they are, the currently available data suggest that accumulation of genomic lesions, rather than their precise order of development with respect to one another, characterize the multistep process of leukemogenesis in which MDS already represent more advanced stages. The prognostic significance of oncogene mutations in MDS patients is controversially discussed. This issue awaits prospective analyses taking into account the influence of treatment modalities. However, the clinical relevance of molecularly defined parameters has already been established for their use as clonal markers in determining the mode of action and efficiency of different therapeutic approaches.
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PMID:Molecular genetic aspects of myelodysplastic syndromes. 161 6

The changes of expression of oncogenes in the mononuclear cells of MDS case was studied during his clinical course, in series. His bone marrow was considered to maintain its function partly in initial stage, since both peripheral blood and bone marrow responded to clinical episodes. However, his hematopoietic function was gradually impaired with the disease evolution to AML. We examined the expression of four oncogenes in the mononuclear cells of his three clinical stages, early RAEB-t, RAEB-t and AML, to study the cause of transformation from MDS to AML. Early RAEB-t cells expressed all oncogenes studied other than c-myb, while only c-myc was weakly observed in RAEB-t. AML cells expressed c-myc, c-jun and c-myb, except for c-fms. The expression of c-fms and c-jun of early RAEB-t was considered to reflect the monocytosis induced by infections, and the expressions of c-myb and c-myc of AML cells were regarded as one of malignant signs of tumor transformation. These findings suggest that the evolutional transformation of MDS to AML was affected by the altered expression of oncogenes.
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PMID:[Altered expression of protooncogenes during clinical course in an AML case transformed from MDS]. 194 45

Recent advances of cytogenetics in human hematological malignancies and solid tumors were reviewed. In leukemia and lymphoma, many non-random chromosome aberrations have been found in the last decade. Further specific chromosome aberrations, which existed usually in less than five percent of acute leukemia cases, were recently found, including t (1 ; 3) in MDS or AML M4, +der (1) t (1 ; 7) in MDS, t (1 ; 11) in AML M4 or M5 and +4 in AML M2 or M4. Recurrent chromosome deletions of 17p-, 9q- and 2p- were also found as secondary aberrations in association with tumor development. Accumulation of the data from variant translocation for the 9 ; 22, 8 ; 21 and 15 ; 17 gave us important informations of critical sites of the chromosome in leukemia development. A new trial for the simultaneous analysis of morphology, immunologic phenotype and karyotype on the same metaphase clearly demonstrated stem cell origin of leukemia in some cases, specializing the affected cell lineage. Progress in non-radioactive in situ hybridization techniques now allows approaches to the recognition of particular chromosome abnormality in metaphase and also in interphase cell by means of specific repetitive probes for each chromosome. Though a hypothesis that fragile sites may act as factors predisposing to chromosomal rearrangements have attracted attention in past few years, recent results appear to be conflicting without any direct proof. Cytogenetic studies in solid tumor have been remarkably progressed with advances of methodology. Recurrent chromosome aberrations in solid tumor were found, such as t (X ; 18) in synovial sarcoma, t (12 ; 16) in liposarcoma, and i (12p) in seminoma. Studies on the correlation between specific chromosome changes and histologic subtypes resulted in an useful orientation to the diagnosis and the therapy. Advance in cytogenetics may serve as new concepts for patho-physiology of malignant tumors and contribute to further understandings of molecular genetics in human solid tumors.
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PMID:[Cancer and chromosomes]. 268 17

Seventeen patients with therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL) were treated with single-agent high-dose cytarabine (HDAC; 1 to 3 g/m2 every 12 hours for 12 doses). The initial neoplasm was still present in eight patients when t-MDS/t-ANLL developed. Fifteen of the 16 patients with chromosomal abnormalities in bone marrow cells had loss or rearrangement of chromosomes 5 and/or 7. One patient had a t(15;17), and one had inadequate material for cytogenetic analysis. Twelve patients had normal metaphase cells (3% to 71%). Indications for HDAC therapy were progressive pancytopenia in 13 patients or rising blast count in four. Five patients died of marrow hypoplasia following therapy. Four others had refractory t-ANLL and died within the subsequent 5 months. Only one of ten patients with a poor performance status (PS greater than or equal to 2 using the ECOG scale) achieved a complete remission, but all seven patients with a good performance status (PS less than or equal to 1) had a complete remission. Hematologic remissions were achieved in 8 patients (47%) after one (6 patients) or two (2 patients) induction courses and were confirmed by recovery of a 100% normal marrow karyotype in six of the seven patients who were retested. Patients in remission received one to four consolidation courses with HDAC alternating with cytarabine/doxorubicin, but seven relapsed within 8 months (median remission duration, 5 months). In every case, the original chromosomal abnormality reappeared at relapse. HDAC has a high response rate for good-performance patients with t-MDS/t-ANLL, but complete remissions are short even when confirmed cytogenetically and consolidated intensively.
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PMID:Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine. 316 10

A phase II clinical trial on MDS was conducted in a cooperative study with orally administrable ara-C analogue, PLAC, which is resistant to cytidine deaminase and had shown an anti-tumor activity on various experimental tumors by oral route. Fifty MDS (3 RA, 18 RAEB, 11 RAEB-T, 18 RAEB-blast crisis (BC) were treated orally with 100 to 400mg/body of daily PLAC. One good response (GR) and 3 partial responses (PR) were obtained in 18 RAEB, and 2 complete remissions, 1 GR and 1 PR were noted in 11 RAEB-T, while 3 PR were seen in 18 RAEB-BC. Overall CR rates were 4%, GR rates 4% and PR rates 14%. Thus, 22% of MDS responded to oral PLAC. No clear daily dose-response was noted. Response, however, was dependent on the treatment period and was obtained in cases which had been treated for more than 20 days. Besides myelosuppression, side effects were mainly gastrointestinal, and anorexia (32%), nausea/vomiting (30%) and diarrhea (8%) were observed. Oral PLAC seems to be active on MDS which does not necessarily require admission to hospital.
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PMID:[Treatment of myelodysplastic syndromes (MDS) with oral administration of N4-palmitoyl-1-beta-D-arabinofuranosyl cytosine (PLAC)]. 338 95

Erythroleukemia was observed in two unrelated cats infected with feline leukemia virus (FeLV) from the same household. Case 1, a 1-year-old neutered male cat developed erythroleukemia (M6) after a diagnosis of myelodysplastic syndrome (MDS-Er) on the criteria of FAB classification of acute leukemias. Case 2, a 1-year-old neutered female cat, which had close contact with Case 1, also developed erythroleukemia (M6Er). In both cases, marked proliferation of erythroid progenitor cells with disproportionally large numbers of immature forms was observed in the bone marrow. In Case 1, neoplastic proliferation of myeloid cells in the bone marrow was also noted at the terminal stage. Combination chemotherapy with daunomycin was partially effective for treatment of these erythroid neoplasias, but did not induce complete remission. Southern blot analysis using exogenous FeLV-specific probes indicated the clonal origin of these hematopoietic tumor cells. Furthermore, the erythroid and myeloid tumor cells in Case 1 were shown to be derived from independent transformed clones. A variant FeLV was shown to be integrated into the tumor cells in Case 1, while a full-length FeLV was found in both cases. Because these erythroid neoplastic diseases occurred in two unrelated cats kept in the same household and these diseases are rare, they may both have been associated with the same FeLV strain.
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PMID:Erythroleukemia in two cats naturally infected with feline leukemia virus in the same household. 749 33

The observation that juvenile chronic myelogenous leukemia (JCML) and childhood bone marrow monosomy 7 syndrome (Mo 7) are similar in many clinical and epidemiologic respects suggests a shared pathogenic basis and raises the possibility that the bone marrows of patients with JCML might lose chromosome 7 alleles by mechanisms that do not result in detectable cytogenetic deletions. We used a series of polymorphic markers mapped to chromosome 7 to test this hypothesis in 22 children with MPS and MDS, including 19 with JCML. All MPS and MDS samples demonstrated allelic heterozygosity with at least one chromosome 7 marker; 16 were heterozygous with probes from both 7p and 7q. Furthermore, the percentage of patient bone marrow samples heterozygous at each locus tested was similar to the frequency observed in the normal population. Whereas these data demonstrate that submicroscopic loss of large segments of chromosome 7 alleles is uncommon in children with MPS and MDS who do not have Mo 7, they do not exclude small deletions around an uncharacterized tumor-suppressor locus. Our results suggest that a number of distinct molecular events contribute to leukemogenesis, and we propose a multistep model to explain the similarities and differences between the major subtypes of childhood MPS and MDS.
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PMID:Molecular evidence that childhood monosomy 7 syndrome is distinct from juvenile chronic myelogenous leukemia and other childhood myeloproliferative disorders. 753 11

We report the application of a combined strategy: chromosome microdissection, degenerate oligonucleotide primed-PCR, and reverse chromosome painting (micro-FISH), as well as forward chromosome painting, for the characterization of chromosomal rearrangements in a MDS patient with the karyotype 46,XX, -11, +r analyzed by G-banding. The karyotype was refined as 46,XX,der(2)t(2;11) (q35;?p13),der(11)dic r(11)(:p13-->q13::p13-->q13:). Our study demonstrated that the chromosome composition of a neoplasia can be identified more systematically and accurately using these combined molecular cytogenetic approaches. The DOP-PCR methodology modified is suitable for the practical application of micro-FISH on specimens prepared for routine banding analysis.
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PMID:The characterization of chromosomal rearrangements by a combined micro-FISH approach in a patient with myelodysplastic syndrome. 755 77

There is compelling evidence that leukemia arises via a multistep process. Molecular analysis of human leukemias, which are typically clonal, commonly shows multiple genetic lesions in a single leukemia including chromosomal translocations, gene amplification, and point mutations, and in several cases the mutational activation of an oncogene and the loss of a tumor suppressor gene have been found in the same leukemic cell. Accumulative evidences suggest that a number of oncogenes and tumor suppressor genes are involved in the hematopoietic tumorigenesis. These mutations can be utilized for molecular diagnosis of human hematopoietic tumors. Among them, detection of chimeric gene generated by chromosomal translocation is especially useful for molecular diagnosis. The t(3;21) (q26;q22) translocation is found usually in blastic crisis of CML and leukemias developed from MDS or hematopoietic proliferative diseases, but never in de novo acute myelocytic leukemia. This raises the possibility that the molecular event underlying the t(3;21) translocation has a critical role in progression from a preleukemic state to a leukemic state. The generation of AML1/EVI-1 chimeric gene has been demonstrated to be consistent in t(3;21)-carrying leukemias. Although target genes remain to be elucidated for both AML1 and EVI-1 as transcription factors, the AML1/EVI-1 fusion protein could work on different set of genes critical to the process of proliferation and differentiation of hematopoietic cells.
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PMID:[Diagnosis of hematological disorders by mutational analysis of oncogenes]. 760 95

This review deals with the differences between leukemias--induced by alkylating agents as opposed to a "new form" of treatment related leukemia due to prior exposure to epipodophyllotoxins the latter having a short treatment--disease onset interval, absence of a MDS phase, a monocytic component and cytogenetic abnormalities involving the 11q23 band. The link between the existence of oncogenes or tumor suppressor genes located on the involved portion of chromosome 11 and the development of epipodophyllotoxin-related leukemia still needs to be examined. Alkylating agents--induced leukemias have a longer treatment--disease onset interval, have a prior myelodysplastic syndrome, and are most frequent myeloblastic or myelomonocytic in nature. Karyotype analysis reveals partial or complete deletion of chromosomes no. 5 or 7. This form of leukemia is highly resistant to treatment in the majority of cases. Some of the possible molecular mechanisms of leukemogenesis are discussed.
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PMID:A comparative analysis of alkylating agent and epipodophyllotoxin-related leukemias. 822 Jan 58


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