Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D03343 (MDS)
 2,225 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

According to the FAB classification, a patient (case 1) could not be diagnosed as MDS-RA, although she had clinical features of MDS, as compared with another patient (case 2) who was diagnosed as RAS and had abnormal karyotype (20q- and 5q-) of bone marrow (BM) cells. BM cells of the two patients were SCD (sister chromatid differentiation) negative. Rearrangement of c-erbB and c-erbA was found in the genome of the BM cells in both patients, when southern blot hybridization was performed with probe v-erbB+A. Therefore, case 1 could be diagnosed as preleukemia. During a period about 3 years of treatment with the drug stanozolol in case 1 there was good effect and successful reversion was obtained. She had then normal hematologic and cytogenetic patterns of BM and PB and the rearrangement of c-erbB of BM cells also disappeared. She has worked for two years since then. The mechanism of effective treatment and successful reversion was discussed briefly. Probe v-erbB was shown to be useful in investigation of gene diagnosis of preleukemia or MDS (shown elsewhere).
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PMID:[Gene diagnosis and successful reversion in a patient with preleukemia]. 130 46

Material from 63 cases with primary myelodysplastic syndromes (P-MDS) (French-American-British [FAB] types: refractory anemia [RA] = 21; RA with ring sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent FAB criteria were not applicable) was analyzed for bone marrow histologic and immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin (H&E) and reticulin stains were used for morphologic assessment. To identify the cell lineage precisely, chloroacetate esterase staining and an indirect immunoperoxidase technique using mouse monoclonal antibodies CD15, CD68, HLA-DR, and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on formalin-fixed paraffin embedded bone marrow biopsies (BMB). The immunohistochemical assessment permitted accurate identification of dysplastic features such as mononuclear and binuclear megakaryocytes, Pelger-Huet neutrophils, and binuclear erythroblasts. Additional bone marrow histologic and immunohistochemical features observed were heterogeneity of immunohistochemical staining in various cell lineages, megakaryocytic emperipolesis, alteration of bone marrow microarchitecture, intravascular clusters of hematopoietic cells, and the types of benign lymphoid aggregates. The nature of abnormally localized immature precursors (ALIP) was discerned. Three types of clusters of immature cells were found that were difficult to distinguish on Giemsa and H&E morphology, these were erythroid aggregates (n = 18); megakaryocytic aggregates (n = 4), and immature granulocytic and monocytic aggregates (n = 32). The bone marrow histologic and immunohistologic patterns permitted the identification of four groups of clinical relevance: Group 1, cases with predominant erythroid hyperplasia and without ALIP (n = 15); group 2, cases with prominent myeloid hyperplasia and presence of ALIP (n = 32); group 3, cases with hypoplastic MDS (n = 10); and group 4, cases with hyperfibrotic MDS (n = 6). Statistical analysis showed a significant difference in survival and leukemic transformation between groups 1, 2, 3, and 4, with cases in group 2 showing the worst prognosis with early death due to increased propensity to leukemic transformation and cytopenia-related complications (P less than .0001). We conclude that immunohistochemistry is feasible on routinely processed BMB and the information obtained is of diagnostic and prognostic importance in P-MDS. The phenotype of ALIP varies with the morphologic and histologic subtypes of MDS and the term should be reserved for cases in whom the clusters in the intertrabecular region are of myeloid (granulocytic and monocytic) lineage on immunohistochemistry.
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PMID:Primary myelodysplastic syndromes: diagnostic and prognostic significance of immunohistochemical assessment of bone marrow biopsies. 137 Feb 3

We describe the clinicomorphological features in 33 cases of primary myelodysplastic syndrome classified according to the FAB classification which presented to a single centre over a 12 year period. Presenting features were typically related to pancytopenia although hepatosplenomegaly and granulocytic sarcomas were far more prevalent than in the adult population. Morphological assessment of the peripheral blood and the bone marrow showed seven patients had refractory anaemia (RA), 13 patients had RA with excess of blasts (RAEB), nine patients had RAEB in transformation (RAEB-t) and four patients had chronic myelomonocytic leukaemia (CMML). The overall mean survival was short (9.9 months) in all the subgroups and the leukaemic transformation rate was high. None of the patients scored 0-1 according to the Bournemouth Scoring System; four patients scored 2 whereas 29 patients scored 3 to 4. We conclude that unlike adults, the myelodysplastic syndromes in children run an aggressive clinical course, irrespective of the FAB subtype, and the pathogenesis of these diseases in paediatric practice warrants scientific scrutiny. Intensive chemotherapy such as the one used in de novo-AML lead to complete remission in some children and these early results suggest that this should be the treatment of choice in paediatric MDS.
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PMID:Primary myelodysplastic syndrome in children: the clinical experience in 33 cases. 141 17

The frequency of non-clonal structural and numerical chromosome aberrations in peripheral blood lymphocytes of 51 patients with MDS and 37 age-matched hematologically normal subjects is assessed. The frequency of aneuploid cells (p less than 0.001) and of structural aberrations (p less than 0.005) was significantly higher in MDS patients than in normal subjects, but showed no relationship with FAB type or with the presence of clonal karyotype abnormalities in the bone marrow. Exchange configurations were only observed in MDS patients (27.5%). The data also suggest that there may be an association between high peripheral blood aberration levels and rapidly progressive disease. This may indicate increased mutagen sensitivity and have implications for treatment.
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PMID:Peripheral blood chromosome aberrations in MDS. 158 82

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

Childhood MDS comprises a group of heterogeneous clinical disorders with overlapping features and many similarities to adult MDS. Environmental factors, genetic predisposition, certain viral infections, and impairment of the developing immune system perhaps play a major role in the genesis of the most common disease forms, such as JCMMoL and the monosomy 7 syndrome. One intriguing finding in these disorders is the striking male predominance. Diagnostic difficulties occur because dysplastic manifestations of the hematopoetic systems are usually not as impressive as in adults and because myelodysplastic and myeloproliferative disease forms overlap considerably. Despite these problems, we believe that pediatric cases of MDS should also be classified according to the established FAB classification for MDS. However, as has already been proposed earlier by others, JCMMol clearly should be considered as a specific entity different from the adult form of CMMoL. As has been shown by cell culture studies, JCMMoL is characterized by the presence of neoplastic macrophage/monocyte progenitor cells. These cells produce several factors that result in autostimulation and suppression of normal hematopoiesis. MDS is a highly malignant disease in children and evolves to acute leukemia after a short period. During the early phase of the disease, supportive care is sufficient. If a compatible donor is available, BMT is the treatment of choice and should be performed during the early stage of disease progression after clinical remission is obtained with chemotherapy. If BMT is not feasible, intensive chemotherapy may improve the clinical condition and prolong survival. Preliminary data suggest that the incorporation of hematopoietic growth and/or differentiation factors in chemotherapy and BMT protocols may have some beneficial effects. The only way to accumulate sufficient data on MDS in children with respect to clinical features, prognosis, and efficacy of treatment is to follow a uniform diagnostic and treatment program. To achieve substantial improvements in the management of childhood MDS, multicenter trials will be essential.
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PMID:Experience in pediatric myelodysplastic syndromes. 161 11

A female patient in whom acute nonlymphocytic leukemia (ANLL, FAB-M6) developed during treatment of hepatocellular carcinoma (HCC) is described. Two years after partial hepatectomy and subsequent chemotherapy, leukemia developed following a 2 month preleukemic stage. Chromosomal analysis revealed an abnormal karyotype, 46,XX,-5, + der(5)t(3;5)(q25;q31). The balanced translocation t(3;5) has been observed in all types of ANLL and MDS except for ANLL M3 subtype. We summarize patients with ANLL M6 and t(3;5).
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PMID:Acute erythroleukemia with t(3;5) accompanied by hepatocellular carcinoma. 166 Jul 36

Clinical, haematological, cytogenetic features and therapeutic problems of 51 patients with MDS were examined. Patients were distributed in 5 FAB subgroups: RA 21, SA 7, RAEB 8, RAEB-t 9 and MMCL 6 patients. Leukaemic transformation occurred in 3 RA, 3 RAEB, 7 RAEB-t and 3 MMCL patients. No SA patient suffered from leukaemic transformation. Cytogenetic alterations occurred in 13 of 29 examined patients; 5q- was the most common abnormality. We did not find any relation between chromosomal anomalies and FAB subgroups. Leukaemic transformation, however, was more frequent in patients with cytogenetic aberrations. In some cases it was not easy to determine the precise diagnostic allocation according to FAB subgroups; it is possible, however, to subdivide MDS prognosis into 2 classes. The more satisfactory therapy of leukaemic transformation is often due to low doses of Ara-C; this therapy allowed a better survival and sometimes to obtain CR which in a M6 ANLL patient continued for 24 months.
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PMID:Myelodysplastic syndromes: analysis of 51 cases. Therapy with low doses of arabinosyl cytosine of leukaemic transformation. 169 90

In a retrospective study, 45 (19.4%) out of 232 patients with MDS revealed myelosclerosis (MS) in bone marrow biopsy (BMB). Histological classification according to FAB criteria showed the following distribution: RA 21 (47%), RARS 1 (2%), RAEB 9 (20%), RAEB-T 3 (7%), and CMMol 11 (24%). Sclerosis occurred in all subtypes of MDS, but with a higher incidence in CMMol. Clinical data showed lower values of hemoglobin and lower platelet counts in MDS.MS. Life expectancy was reduced to 7.8 months, compared with 15.0 months in MDS without MS (p = 0.0026). In RA, the survival times were 9.7 months in MDS.MS, compared to 27.9 months in MDS without MS (p = 0.0035). 21 (47%) of the patients with MDS.MS experienced a transformation into ANLL. Myelosclerosis therefore seems to herald a bad prognosis.
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PMID:[Myelosclerosis in myelodysplastic syndromes (MDS). Retrospective analysis of 232 patients with MDS]. 170 73

This is a review of preleukaemic states in children. In a prospective series of 109 children with AML the overt disease was preceded by MDS in 22 cases. Ten of these patients had Down's syndrome. Advanced FAB groups were represented in the series. An important subgroup is the bone marrow monosomy 7 syndrome. Cytogenetic anomalies are common in MDS, and multiple and complicated abnormalities develop in nearly all patients with progressing disease. Some children die before transformation to overt ANLL. Transformation usually occurs, few children survive. With cytostatic treatment the risk of irreversible aplasia is great. The choice of schedule should therefore be carefully considered. Bone marrow transplantation has proved beneficial in a number of cases, but these are still quite few. The dysfunction of the bone marrow preceding ALL is due to transient aplastic anaemia--spontaneous remission--overt ALL, often FAB type L1, immunophenotype CALLA. The ALL reacts to the same treatment as de novo ALL of the same type and the prognosis is the same.
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PMID:Bone marrow dysfunctions preceding acute leukemia in children: a clinical study. 173 77


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