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)

Chronic myeloproliferative disorders (CMPD) are neoplastic disorders of the hematopoietic stem cell. Four different entities are defined: chronic myeloid leukemia (CML), polycythemia vers, essential thrombocythaemia, and idiopathic myelofibrosis. In addition, overlapping entities within the CMPDs and between CMPDs and myelodysplastic syndrome have been described. Diagnostic measures are performed to classify the subtype exactly and to assess risk factors and prognosis. Cytogenetic and molecular analyses are mandatory for the characterization of the malignant clone. Hydroxyurea and interferon-alpha have proven effective in all CMPE. In CML, specific inhibition of the elevated ABL tyrosine kinase activity with imatinib is associated with high response rates. Allogeneic stem cell transplantation is the only curative treatment option for all entities. In CML, the decision-making analysis should be based on established scores. In BCR-ABL negative CMPDs an allogeneic stem cell transplantation should only be performed in patients with unfavorable prognosis.
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PMID:[Chronic myeloproliferative diseases. Diagnosis and therapy]. 1467 16

Myeloproliferative disorders (MPDs) are chronic conditions that require long-term treatment. MPDs have been considered neoplastic disorders that have a propensity to transform to acute leukemia or myelodysplastic syndrome. One of the MPDs, chronic myeloid leukemia (CML), has the distinct cytogenetic abnormality of the Philadelphia chromosome. In CML, transformation to acute leukemia is a common occurrence, with the timeline measured in years rather than decades. With the other three disorders from this group, polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF), transformation to acute leukemia is less frequently seen and, although variable, can take a longer period of time. The choice of therapy used for MPDs may contribute to leukemic transformation; chlorambucil, busulfan, and radiophosphorus are all examples of therapy that have been shown to be leukemogenic. Several studies have suggested the potential leukemogenicity of hydroxyurea (HU), but this remains controversial because no randomized studies have been conducted. The two newest agents used for MPDs, interferon-alpha and anagrelide, have both been studied for efficacy, but their influence on the potential for leukemic transformation has not been well studied to date.
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PMID:Treatment paradigms in the management of myeloproliferative disorders. 1519 May 19

Susceptibility to apoptosis varies in different forms of myelodysplastic syndromes (MDS). Our in vitro study aimed at better defining the cell kinetic profile by investigating whether G-CSF and interferon-alpha (IFNalpha) were capable of controling apoptotic/proliferative mechanisms in RAEB as well as in RAEB-t forms. Apoptosis and cell-cycle distribution were measured in mononuclear and in CD34+ cells from bone marrow samples of 27 MDS patients with RAEB (n = 15) and RAEB-t (n = 12). In selected samples, the in vitro influence of G-CSF and lymphoblastoid (Ly)-IFNalpha on the apoptotic susceptibility and on the cell kinetics of the above MDS populations was evaluated. RAEB samples showed a significantly greater apoptosis than RAEB-t ones, both in mononuclear cells (14.76%+/-8.73 vs. 5.95%+/-3.88, P= 0.0058) and in CD34+ cells (24.66%+/-16.08 vs. 3.96%+/-2.57, P = 0.0007). Short-term cell culture in the presence of G-CSF reduced apoptosis in CD34+ cells in all 4 RAEB samples tested (39.1%+/-40.7 vs. 21.0%+/-23.5, P = n.s.); the percentage of cells in S-phase significantly increased in 3/4 samples (19.90%+/-4.40 vs. 32.40%+/-7.85, P = 0.03). Ly-IFNalpha protected CD34+ cells from apoptosis in 3/4 RAEB samples (25.7%+/-8.06 vs. 10.9%+/-8.8, P = n.s.), but did not modulate cell-cycle distribution. G-CSF and Ly-IFNalpha failed to affect apoptosis and proliferation in RAEB-t. These observations indicate that in RAEB forms increased apoptosis can be efficiently counteracted in most of the samples by both G-CSF and Ly-IFNalpha, suggesting that only in these forms a retained regulatory mechanism on the apoptotic/ proliferative balance may allow therapeutic intervention with apoptotic regulators.
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PMID:Apoptosis susceptibility and cell-cycle distribution in cells from myelodysplastic syndrome patients: modulatory in-vitro effects of G-CSF and interferon-alpha. 1535 45

Mastocytosis is characterized by mast cell proliferation that may be limited to the skin (cutaneous mastocytosis) or may involve one or more extracutaneous organs, e.g., the bone marrow (systemic mastocytosis; SM). This study objective is to evaluate the features and outcome of patients referred to M. D. Anderson Cancer Center (MDACC) with SM. A search of the MDACC database from 1944 to 2002 was conducted for patients with SM and review of their clinical charts. Eighteen patients with mastocytosis were identified in the MDACC database; 15 (11 males and 4 females) had SM and available information. Two had associated myelodysplastic syndrome (MDS), and one had acute myeloid leukemia (AML). The median age was 58 years (range 31-80). Nine patients were treated with subcutaneous interferon-alpha, and only 1 experienced temporary control of the disease. Three of these patients were then treated with imatinib mesylate: transient improvement was noted in two patients. One patient underwent stem cell transplantation as first therapy and achieved complete remission; this patient had associated MDS and is now in complete remission for 8 years. The patient with associated AML was treated with high-dose cytarabine and idarubicin; he has been in complete remission for 16 months. One patient was treated with induction chemotherapy consisting of high-dose cytarabine and 2CDA but expired due to sepsis. Three patients received symptomatic therapy only; these were the only 3 patients who presented with normal blood counts. SM is rare and has no effective standard of care. Collaboration among academic centers to accrue enough patients to evaluate novel therapeutic strategies is needed.
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PMID:Management of patients with systemic mastocytosis: review of M. D. Anderson Cancer Center experience. 1549 58

Treatment of chronic myeloid leukemia (CML) with imatinib (Gleevec) induces a much higher rate of partial and complete cytogenetic responses (CCR) than interferon-alpha (IFN)-based therapies. Conventional wisdom suggests that elimination of the Philadelphia (Ph)- positive cells will lead to re-establishment of normal Ph-negative hematopoiesis. Surprisingly, karyotypic abnormalities were detected in the chromosome negative cells of some patients with cytogenetic response to imatinib. In some cases, this was associated with a myelodysplastic syndrome (MDS). While clonal evolution in Ph-positive cells is considered part of the progression of CML, clonal evolution in Ph-negative cells had been observed only rarely in a small number of patients treated with IFN or bone marrow transplantation, raising the question whether the phenomenon may be causally linked to imatinib therapy. In this manuscript, we will review the currently available data, suggest possible causes and discuss potential implications for patient management. We are fully aware that a systematic study of a larger patient cohort will be required to conclusively address these issues.
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PMID:Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in chronic myeloid leukemia patients treated with imatinib. 1551 7

We describe a case of systemic mastocytosis associated with myelodysplastic syndrome. The bone marrow showed multifocal clusters of mast cells and myeloid dysplasia. Sequencing of the KIT DNA revealed a point mutation at codon 816 including a substitution of valine for aspartic acid (D816V). The patient's tumor did not respond to imatinib; however, interferon-alpha reduced the bone marrow mast cells and serum total tryptase. The patient remains alive at one year after the diagnosis without disease progression.
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PMID:Successful treatment of KIT D816V-positive, imatinib-resistant systemic mastocytosis with interferon-alpha. 1991 99


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