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

Myelodysplastic syndrome (MDS) is a monoclonal disorder of the pluripotent stem cell that frequently evolves into acute leukemia. MDS is characterized by trilineage dysplasia and by ineffective hematopoiesis. The etiology of MDS is poorly understood. However, the frequent association of chromosomal abnormalities (deletions, inversions, translocations, trisomies and monosomies) with MDS suggests that an oncogene, or a tumor suppressor gene might be involved in the pathogenesis and evolution of this disorder. This review summarizes the clinical, laboratory, chromosomal and prognostic findings of some of the cytogenetic abnormalities such as; 20q deletion, chromosome 5, 7 and 3 abnormalities, 17p-syndrome, trisomy 8, and loss of Y chromosome. In addition, this review goes into the discussion of the most recent development in the field of molecular biology to understand some of the mechanisms resulting in the development and progression of MDS.
 ...
PMID:Myelodysplastic syndrome: review of the cytogenetic and molecular data. 1173 46

A serious complication of aplastic anemia (AA) is its evolution to clonal hematologic diseases such as myelodysplasia (MDS) and leukemia, which is usually associated with the appearance of a cytogenetic abnormality in bone marrow cells. We present here an analysis of a cohort of 30 patients with otherwise typical AA in whom clonal karyotypic evolution was observed during frequent periodic marrow examinations. The actuarial risk for this complication has been estimated in other studies at around 15% at 5 years. Conversion from normal to abnormal karyotype occurred at a constant rate after initial diagnosis, with about 50% of cases developing within the first 30 months. Transient chromosomal abnormalities were infrequent. Clinically, AA patients with clonal cytogenetic patterns were heterogenous; a variety of karyotypic defects with numerical and structural abnormalities of chromosome 7 accounted for 40% of all cases followed by trisomy 8, structural and numerical abnormalities of chromosome 13, deletion of Y chromosome, and complex cytogenetic abnormalities. Unlike in primary MDS, aberrancies of chromosome 5 and 20 were infrequent. The clinical course depended on the specific abnormal cytogenetic pattern. Most deaths related to leukemic transformation occurred in patients with abnormalities of chromosome 7 or complex cytogenetic alterations or both. Evolution of chromosome 7 abnormalities was seen most often in refractory patients who had failed to respond to therapy. In contrast, trisomy 8 developed in patients with good hematologic responses who often required chronic immunosuppression with cyclosporine A (CsA), and survival was excellent. Although AA patients with monosomy 7 showed a similar prognosis to those with primary MDS, trisomy 8 in AA appears to have a more favorable prognosis than in MDS.
 ...
PMID:Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. 1196 74

Trisomy 15 as the sole autosomal anomaly is uncommon in hematological malignancies but could be preferentially associated with myelodysplasia. We report a 61-year-old man who developed pancytopenia following two courses of chemotherapy for chronic lymphoid leukemia. Cytogenetic studies at diagnosis of pancytopenia with R banding showed a 47,XY, + 15[3]/45,X[3]/46,XY[14] karyotype. A review of the 53 cases of myelodysplastic syndromes (MDS) and myeloid related disorders associated with trisomy 15 reported in the literature showed that 18 of the 31 men also lost the Y chromosome in the trisomic 15 cell line. Their mean age was significantly higher than that of males who had not lost the Y chromosome (p < 0.05). The main feature of the patient reported here is the presence of two abnormal cell lines, one having lost the Y chromosome, the other having gained a chromosome 15. Therefore, the two events occurred independently, the loss of the Y chromosome being possibly due to aging and the trisomy 15 to the hematologic disorder.
 ...
PMID:Trisomy 15 as the sole abnormality in myelodysplastic syndromes: case report and review of the literature. 1268 32

Donor-cell-derived hematopoietic malignancy is a rare event after bone marrow transplantation. Most cases in the literature occurred within the first year. We present a rare case of a female patient who had a bone marrow transplant for severe aplastic anemia (SAA) at the age of two and a half years from her human leukocyte antigen-identical brother. She developed a myelodysplastic syndrome (refractory cytopenia with multilineage dysplasia) 12 years later. Initially, the malignant clone was of recipient origin, but within several months, progression to a clinically more aggressive refractory anemia with excess blasts (RAEB) was accompanied by the outgrowth of a new clone of donor origin. In this report we provide evidence proving that the patient's final malignant clone arose in donor cells: cytogenetic analysis of the marrow showed a male karyotype and a t(3;21)(q26;q21) in all 62 metaphases analyzed. Interphase fluorescence in situ hybridization showed that all identifiable cells contained the Y chromosome. We conclude that donor-cell-derived hematopoietic malignancy after bone marrow transplantation can occur even after many years. We believe that the 13 years that elapsed between the transplant and the development of RAEB in our case represent the longest latency period in the literature.
 ...
PMID:Donor-cell myelodysplastic syndrome developing 13 years after marrow grafting for aplastic anemia. 1269 88

Cytogenetic analysis can be important in determining the prognosis and diagnosis of a number of hematological disorders, including myelodysplastic syndromes (MDS). Here, we compared metaphase chromosomal analyses on bone marrow aspirates from MDS patients with interphase fluorescence in situ hybridization (FISH) using probes specific for chromosomes nos. 5, 7, 8, 11, 13 and 20. Forty-three patients enrolled in ECOG protocol E1996 for low risk MDS and five patients enrolled in ECOG protocol E3996 for high risk MDS were studied by both metaphase chromosomal analysis and interphase FISH. Excluding those with a clonal loss of the Y chromosome, an abnormal clone was detected by cytogenetic analysis in 18 of 48 samples (37.5%). In comparison, our FISH panel detected an abnormal clone in 17 of 48 samples (35.4%). Twenty-nine of 30 samples with apparently normal karyotypes, including those with a missing Y chromosome, were also normal by our FISH panel. One patient had an occult deletion of chromosome 11 that was detected by FISH. These results indicate that around 60% of patients with MDS do not have abnormalities that are detectable by either chromosomal or FISH studies. In addition, it appears that interphase FISH studies are nearly as sensitive as cytogenetic analyses and can be a useful tool in studying bone marrow aspirates where cytogenetic analysis is not possible.
 ...
PMID:Comparison of interphase FISH and metaphase cytogenetics to study myelodysplastic syndrome: an Eastern Cooperative Oncology Group (ECOG) study. 1292 44

The case of a 32-year-old female with relapsed myelodysplastic syndrome (MDS) after second course of allogeneic transplantation is described. The peripheral blood stem cell transplantation was performed as early as 3 months after the initial bone marrow transplantation because of rejection and relapse; however, the patient again relapsed 2 months later. Immediate discontinuation of cyclosporine resulted in the progression of pancytopenia and the development of high fever, liver dysfunction and skin eruption. The patient was then treated with dexamethasone, which successfully stabilized these symptoms. After these clinical events, a dramatic hematological response was obtained; the blast rate was reduced from 10.6 to 0% in bone marrow aspiration, and pancytopenia was restored to normal levels. Moreover, fluorescence in situ hybridization analyses with X and Y chromosome-specific probes revealed that hematopoietic precursor cells were predominantly of donor origin. The patient subsequently received donor lymphocyte infusion (DLI) from the original donor. Currently, 2 years after DLI, the patient continues to be in remission.
 ...
PMID:[Sustained remission of MDS overt leukemia associated with abrupt discontinuation of immunosuppression following relapse after the second course of allogeneic hematopoietic stem cell transplantation]. 1468 72

The diagnosis of myelodysplastic syndrome (MDS) is difficult to establish based on morphologic features alone because dysplasia may not always be detectable and the presence of dysplasia is not itself evidence of clonal disorder. As a result, the detection of a clonal cytogenetic abnormality has a major role in difficult cases in regard to diagnosis and the recognition of morphological cytogenetic correlates. In an attempt to assess the frequency and characteristic type of abnormal clones when it is not clear whether or not a hematological condition is neoplastic, cytogenetics have been analyzed necessarily in 159 patients with unexplained cytopenia or suspected MDS. We found 14 patients (8.8%) with cytogenetic abnormalities in the absence of concomitant dysplastic features of the marrow at diagnosis. The cytogenetic changes were characteristic of those reported for myeloid malignancies: 3 del(20q), 2 Y chromosome losses, 2 del(5q), 2 11q23 abnormalities, and one each of t(3;5), i(7q), trisomy 8, and del(13q). One case of ring chromosome 4 was also found. A few months later, 3 of these patients showed marrow changes consistent with MDS. Our data demonstrated that a significant proportion of otherwise uncertain diagnoses presented abnormal clones. Long-term follow-up will be required to help determine the malignant potential of these clones.
 ...
PMID:Karyotypic identification of abnormal clones preceding morphological changes or occurring with no definite morphological features of myelodysplastic syndrome: a preliminary study. 1735 78

The Udegeys are a small ethnic group who live along the tributaries of the Amur River Basin of southeastern Siberia in Russia. They are thought to speak a language belonging to a subdivision of the Tungusic-Manchu branch of the Altaic family. To understand the genetic features and genetic history of the Udegeys, we analyzed two haploid markers, mitochondrial DNA (mtDNA), and Y-chromosomal variation, in 51 individuals (including 21 males) from the Udegey population. In general, the Udegeys' mtDNA profiles revealed similarities to Siberians and other northeastern Asian populations, although a moderate European contribution was also detected. Interestingly, pairwise values of F(ST) and the MDS plots based on the mtDNA variation showed that the Orok and Nivkh inhabiting the very same region of the Udegey were significantly different from the Udegey, implying that they may have been isolated and undergone substantial genetic drift. The Udegeys were characterized by a high frequency (66.7%) of Y chromosome haplogroup C, indicating a close genetic relationship with Mongolians and Siberians. On the paternal side, however, very little admixture was observed between the Udegeys and Europeans. Thus, the combined haploid genetic markers of both mtDNA and the Y chromosome imply that the Udegeys are overall closest to Siberians and northeast Asians of the Altaic linguistic family, with a minor maternal contribution from the European part of the continent.
 ...
PMID:Genetic diversity of two haploid markers in the Udegey population from southeastern Siberia. 1995 29

The clone size has been postulated as a prognostic factor in myelodysplastic syndromes (MDS), though it has not been studied systematically. We tested its impact (<100% vs. 100%) in a population of 216 MDS with chromosome 7 abnormalities (-7/7q-) (n=84), trisomy 8 (n=99), 20q deletion (n=28) and loss of Y chromosome (n=26). Focusing on the survival the bad prognosis of -7/7q- was independent of the clone size (9.3 vs. 5.0 months, P=0.188, not significant) but trisomy 8 cases with 100% aberrant metaphases did reveal a worse prognosis (13.9 vs. 5.9 months, P=0.003).
 ...
PMID:Clinical impact of the clone size in MDS cases with monosomy 7 or 7q deletion, trisomy 8, 20q deletion and loss of Y chromosome. 2126 92

Myelodysplastic syndromes (MDS) include a group of heterogeneous hematological disorders with a variable risk of leukemic evolution and short survival. Around 40-50% of patients show abnormal karyotypes that are mostly characterized by monosomies or deletions. Cytogenetic findings are an independent prognostic factor and the International prognostic scoring system (IPSS) differentiates three cytogenetic categories, despite the Intermediate one being heterogeneous. The aim of this study, including 421 Argentinean patients with primary MDS, is to characterize the cytogenetic profile, to test its prognostic value and to compare partial and monosomal karyotypes against other cytogenetic findings. An abnormal karyotype (median survival: 26 months) was observed in 176 patients. The presence of complex karyotypes, number of alterations, and the IPSS cytogenetic groups showed significant differences for predicting outcome. Behavior of patients with isolated deletions (median survival: 49 months) did not differ from those with normal karyotype (56 months, P = 0.654) or Good prognostic findings (43 months, P = 0.371). However, a worse prognosis was observed when another alteration was added (31 months, P = 0.043). Karyotypes with autosomal monosomies (median survival: 16 months) had a prognostic impact similar to other Poor cytogenetic findings (17 months, P = 0.626). In our population classified according to French-American-British (FAB) or World Health Organization (WHO), this new categorization of cytogenetic abnormalities, recognizing three different risk groups, showed an independent prognostic impact and a better discriminating power than the IPSS categories. It can be concluded that all isolate deletions (excluding 7q-) are good prognostic findings and all monosomies (excluding Y chromosome loss) are bad indicators.
 ...
PMID:Partial and total monosomal karyotypes in myelodysplastic syndromes: comparative prognostic relevance among 421 patients. 2167 72


<< Previous 1 2 3 4 Next >>