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)

At 6 months of age, the patient was diagnosed as having neuroblastoma stage IV and was given the chemotherapy, local irradiation, and operation. The treatment was completed in September 1989. In 1992, at 6 years of age, her height was -3 SD and growth hormone secretion was depressed. She had been supplemented with recombinant human growth hormone (rhGH). Because the white blood cell counts began to decrease gradually in 1993, the rhGH therapy was interrupted on January 19, 1994. The rhGH supplement was resumed after a 3-month interval because of the parent's desire. Pancytopenia soon became apparent. She was diagnosed as having myelodysplastic syndrome (MDS) as a refractory anemia with an excess of blasts in transformation with monosomy 7. The rhGH therapy was interrupted again, without any improvement of the MDS. In culture studies, neither rhGH nor insulin-like growth factor-1 stimulated proliferation of her bone marrow cells. These data suggested that the treatment with rhGH after the chemotherapy played some role in the promotion, but not acceleration, of the MDS.
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PMID:Myelodysplastic syndrome during recombinant human growth hormone supplementation after treatment for neuroblastoma. 894 Jul 42

The insulin-like growth factor (IGF) system regulates proliferation and differentiation of hematopoietic cells. IGFs exert their effects through specific receptors on growing and differentiating blood cells as they emerge from their small pool of ancestral stem cells. The IGF system is complex as both stimulating and inhibiting effects occur by interaction of IGFs and IGF-binding proteins (IGFBPs). IGFs stimulate erythrocytes and lymphocytes but also promote leukemic hematopoietic cell proliferation. IGF-I appears to be correlated with hemoglobin levels in anemia and could also be of benefit for patients with bone marrow aplasia after transplantation. Hypersensitivity to IGF-I has been implicated as an underlying cause of polycythemia vera. Loss of imprinting of IGF-II is found in acute myeloid leukemia and myelodysplastic syndrome. Apoptosis of hematopoietic cells is significantly reduced by IGF-I involving an intriguing signal transduction pathway. IGFs could therefore, although not classical hematopoietic growth factors, be of benefit for patients with diverse hematopoietic disorders.
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PMID:The insulin-like growth factor system in hematopoietic cells. 1200 50

During the past years, several independent laboratories have highlighted the presence of nuclear signaling pathways based on lipid hydrolysis, which are not a mere duplication of those occurring at the plasma membrane. Among the enzymes of the cycle, nuclear phosphoinositide-specific phospholipase C (PI-PLC) has been analyzed quite extensively. In this context, PI-PLCbeta1 appears to play a key role as a check point in the G1 phase of the cell cycle. It has also been shown that its activation and/or up-regulation is upon the control of type 1 insulin-like growth factor receptor (IGF-R) in both mouse fibroblast and myoblasts, suggesting that its signaling activity is essential for the normal behavior of the cell, at least in culture. The recent discovery of a possible involvement of the deletion of PI-PLCbeta1 gene in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) in humans strengthens the contention that nuclear PI-PLC signaling is essential for physiological processes such as cell growth and differentiation. Even though PI-PLCbeta1 is present and does not translocate to eukaryotic nuclei, this organelle, even though only in some conditions contains also PI-PLCgamma1 which acts not only as a PI-PLC but also as guanine nucleotide exchange factor (GEF) for PI 3-kinase enhancer (PIKE) and is somehow linked to PI 3-kinase (PI3K) activity. Also members of PI-PLCdelta family are shuttling from the nucleus to the cytoplasm and return and are possibly involved in the control of cell growth. We must also take into account the presence in the nucleus of other phospholipases such as phospholipase A2 (PLA2) and phospholipase D (PLD), which also exert a signaling activity upon external stimuli. On the whole this review highlights the latest development in the PI-PLC cycle in the nucleus, which in terms of activation, regulation and down-stream targets differs substantially from that located at the plasma membrane.
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PMID:Nuclear phospholipase C: involvement in signal transduction. 1589 48

To explore the expression of insulin-like growth factor receptor type I (IGF-IR) and its relationship to apoptosis in hematopoietic cells of MDS and AML marrow, bone marrow nucleated cells from 16 patients with myelodysplastic syndrome (MDS) and 16 patients with acute myeloid leukemia (AML) were collected for analysis, respectively. Another 16 normal donors' marrow samples were taken as controls. Immunocytochemical method (APAAP) and TdT-mediated dUTP nick end labeling (TUNEL) fluorescence were used simultaneously on cytospins of nucleated cells from these patients. Then, the ratios of IGF-IR positive cells and apoptosis cells in all nucleated cells were counted separately. The results showed that (1) there was a higher IGF-IR expression rate (56.8 +/- 14.3)% in nucleated cells of MDS marrow than that in normal marrow (40.4 +/- 9.6)% (P < 0.01). Also IGF-IR positive rate in AML marrow (86.8 +/- 13.8)% was significantly higher than that in normal marrow (P < 0.01). Furthermore, IGF-IR had higher expression in AML marrow when compared to MDS marrow (P < 0.01); (2) apoptosis in nucleated cells of MDS marrow (5.4 +/- 3.0)% was significantly higher than that in normal marrow (1.2 +/- 0.9)% (P < 0.01) and AML marrow (0.3 +/- 0.4)% (P < 0.01), while there was less apoptosis in AML marrow than that in normal marrow (P < 0.01); (3) apoptosis occurred mainly in IGF-IR negative cells (9.0 +/- 4.8)% and less in IGF-IR positive cells (1.4 +/- 2.4)% (P < 0.01). IGF-IR expression showed negative correlation with apoptosis (r = -0.852, P < 0.01); (4) IGF-IR of MDS nucleated cells in RAEB/RAEB-t/CMML expressed higher than that in RA/RAS (64.1 +/- 3.2% vs 53.5 +/- 16.2%) subgroup, although no significant difference was found (P > 0.05); and apoptosis in RAEB/RAEB-t/CMML subgroup was lower than that in RA/RAS cases (3.1 +/- 2.1% vs 6.4 +/- 2.8%) (P < 0.05); (5) IGF-IR positive rate in nucleated cells of MDS and AML marrow showed positive correlation with blast rate (r = 0.677; P < 0.01). It is concluded that there is overexpression of IGF-IR in marrow nucleated cells in MDS and AML cases. And it seems that the overexpression of IGF-IR may suggest some malignant proliferation tendency and suppress cell apoptosis through some mechanism in these malignant hematologic ailments. So, anti-IGF-IR will become a new approach for therapy of MDS and AML.
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PMID:[Expression of insulin-like growth factor receptor type I in marrow nucleated cells from hematologic malignancies and its anti-apoptotic effect]. 1597 47

To verify the expression of type 1 insulin-like growth factor receptor (IGF-IR) and its impact on hematopoietic cells apoptosis in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), marrow samples from 16 patients with MDS and 16 patients with AML were examined along with 16 healthy donors as controls. Immunocytochemical methods (alkaline phosphatase anti-alkaline phosphatase) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (fluorescence) were used simultaneously on nucleated cell cytospins. The ratio of IGF-IR positive cells and apoptotic cells as well as the relationship between them were then analyzed separately. A quantitative real-time reverse transcriptase-polymerase chain reaction (PCR) was administrated for six MDS cases and two normal controls to validate IGF-IR expression detected by immunochemistry. In our assay, IGF-IR appeared to have higher to lower expression rate in turn from AML (86.8+/-13.8%) to MDS (56.8+/-14.3%) and then to normal controls (40.4+/-9.6%) (P<0.01 between each group). In MDS nucleated cells, IGF-IR showed stronger expression in refractory anemia with excess blasts (RAEB)/RAEB in transformation/chronic myelomonocytic leukemia subgroup when compared to RA/RA with ringed sideroblasts cases (64.1+/-3.2 vs 53.5+/-16.2%) (P>0.05). Nucleated cells from MDS marrow underwent more apoptosis (5.4+/-3.0%) than that in normal marrow (1.2+/-0.9%) (P<0.01) and AML marrow (0.3+/-0.4%) (also, P<0.01 between each compared group). For both AML and MDS cases, apoptotic signals presented mainly in individual IGF-IR negative cells (9.0+/-4.8%) and less so in IGF-IR positive cells (1.4+/-2.4%) (P<0.01). When analyzed by groups, cell number with IGF-IR expression showed a negative correlation to apoptotic cells amount (r=-0.852; P<0.01) but positive correlation to their blast count (r=0.677; P<0.01). Outcome from real-time quantitative PCR appeared to have a trend of enhanced IGF-IR expression in advanced MDS subtypes. In conclusion, overexpression of IGF-IR existed in hematopoietic cells in MDS and AML marrows, which appeared to be contributed to disease progress.
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PMID:Expression of type 1 insulin-like growth factor receptor in marrow nucleated cells in malignant hematological disorders: correlation with apoptosis. 1632 78

Thrombopoietin (TPO) receptor agonists represent a new approach for the treatment of thrombocytopenia, which may develop as a consequence of immune thrombocytopenia, chemotherapy treatment, chronic hepatitis C infection, or myelodysplastic syndromes. There are concerns that use of certain growth factors can hasten disease progression in some types of hematologic malignancies and solid tumors. In this study, expression of MPL (TPO-R) mRNA was examined in tumor cell lines, patient tumor samples (renal cell carcinoma, prostatic carcinoma, soft tissue and bony/cartilage sarcoma, colon cancer, and lymphoma), and normal tissues using microarray analysis and qRT-PCR. MPL mRNA is expressed at very low or undetectable levels compared with erythropoietin receptor (EPOR), human epidermal growth factor (ERBB2; HER2), and insulin-like growth factor-1 receptor (IGF1R) in these patient samples. These data suggest TPO-R agonists will likely preferentially stimulate proliferation and differentiation of cells of megakaryocytic lineage, potentially demonstrating their utility for correcting thrombocytopenia in clinical settings.
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PMID:Thrombopoietin receptor levels in tumor cell lines and primary tumors. 2131 60

As a hormone with a number of biological effects, insulin not only displays the function of classic metabolic regulation, but also can regulate cell proliferation and differentiation, and ensure growth and development of embryos and young individuals. In vitro insulin can stimulate cell proliferation and differentiation. Insulin is also an important growth regulator in vivo, which has been proved in more and more studies. The role of insulin at the cellular level is triggered by the binding of insulin to its receptor located in the cell surface. However, insulin at the higher concentration can also been triggered by insulin-like growth factor-1 (IGF-1) receptor. Its role varies in different cell lines. Insulin receptor and insulin-like growth factor receptor-1 are widely expressed in human MDS and AML cell membranes. Recently, many studies related to the relationship between hyperinsulinemia and cancer have been reported. In this review the role and its possible mechanism in promoting human leukemia cell proliferation and inhibiting human leukemia cell proliferation are summarized. Furthermore, the potential application prospect of insulin analogues also will be described.
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PMID:[Influence of insulin on human leukemia cell proliferation]. 2136 66

Malignant clonal cells purification can greatly benefit basic and clinical studies in myelodysplastic syndrome (MDS). In this study, we investigated the potential of using type 1 insulin-like growth factor receptor (IGF-IR) as a marker for purification of malignant bone marrow clonal cells from patients with MDS. The average percentage of IGF-IR expression in CD34+ bone marrow cells among 15 normal controls was 4.5%, 70% of which also express the erythroid lineage marker CD235a. This indicates that IGF-IR mainly express in erythropoiesis. The expression of IGF-IR in CD34+ cells of 55 MDS patients was significantly higher than that of cells from the normal controls (54.0 vs. 4.5%). Based on the pattern of IGF-IR expression in MDS patients and normal controls, sorting of IGF-IR-positive and removal of CD235a-positive erythroid lineage cells with combination of FISH detection were performed on MDS samples with chromosomal abnormalities. The percentage of malignant clonal cells significantly increased after sorting. The enrichment effect was more significant in clonal cells with a previous percentage lower than 50%. This enrichment effect was present in samples from patients with +8, 5q-/-5, 20q-/-20 or 7q-/-7 chromosomal abnormalities. These data suggest that IGF-IR can be used as a marker for MDS bone marrow clonal cells and using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells.
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PMID:Purification of Bone Marrow Clonal Cells from Patients with Myelodysplastic Syndrome via IGF-IR. 2646 1