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)

The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYK(wt), TEL-SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYK(wt) enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development. ITK-SYK caused lethal T-cell lymphomas and the cytoplasmic TEL-SYK fusion induced an acute panmyelosis with myelofibrosis-type acute myeloid leukemia (AML) with up to 50% immature megakaryoblasts infiltrating bone marrow, spleen and liver, additional MPN features (myelofibrosis and granulocyte expansion) and MDS stigmata with megakaryocytic and erythroid dysplasia. LKS cells were reduced and all subsets (LT/ST/MPP) showed reduced proliferation rates. SYK inhibitor treatment (R788) of diseased TEL-SYK mice reduced leukocytosis, spleen and liver infiltration, enhanced the hematocrit and prolonged survival time, but could not significantly reduce myelofibrosis. Stat5 was identified as a major downstream mediator of TEL-SYK in vitro as well as in vivo. Consequently, targeted deletion of Stat5 in vivo completely abrogated TEL-SYK-induced AML and myelofibrosis development, proving Stat5 as a major driver of SYK-induced transformation. Our experiments highlight the important role of SYK in AML and myelofibrosis and prove SYK and STAT5 inhibitors as potent treatment options for those diseases.
...
PMID:Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice. 2514 22

Neutrophil-to-lymphocyte ratio (NLR) has been proposed as a bone loss index in postmenopausal women and as a marker of inflammation in coeliac patients. The aims of this work were to evaluate the effect of gluten-free diet (GFD) on NLR retrospectively and study the relationship between NLR and Mediterranean diet adherence and selected food groups (fruits, vegetables, red meat, potatoes, and unrefined and refined cereals). Adult individuals (n = 50), who had been on a strict GFD by at least 6 months, were recruited. The degree of adherence to the Mediterranean diet was calculated with two different scores: the Mediterranean Diet Score (MDS-14), assessed through the validated 14-item questionnaire of the PREDIMED study, and the MEDScore (Score-55) proposed by Panagiotakos. The latter includes the consumption of unrefined cereals (UC). High percentages of osteopenia and osteoporosis were found within the recruited subjects, who furnished the reports of bone mineral density (BMD), in particular in postmenopausal (Post-M) women. Recent NLR was higher in subjects with osteoporosis compared to osteopenia and normal BMD. However, retrospective analysis showed both increase and decrease in NLR after GFD, with no significant differences between Marsh grade, anemia, and BMD status. Moreover, premenopausal previous pregnancy (Pre-MPP) and Post-M had higher NLR at diagnosis compared to Men and premenopausal (Pre-M), but higher differences were observed in recent NLR between Pre-MPP and Men only. Chocolate consumption was associated with lower recent NLR, whereas the latter was correlated with Score-55, but not with MDS-14. Moreover, refined cereal consumption was correlated with recent NLR. Although large prospective studies are needed in order to clarify the relationship between UC and NLR in coeliac patients, in this pilot study, we have investigated for the first time the relationship between NLR, dietary habit, and osteoporosis in coeliac disease.
 ...
PMID:Neutrophil-to-Lymphocyte Ratio, Mediterranean Diet, and Bone Health in Coeliac Disease Patients: A Pilot Study. 3132 Sep 84