34 research outputs found
Has melatonin protective effects on irradiated rat pineal gland? cronobiologic and electron microscobic study
Effect of melatonin and time of administration on irradiation-induced damage to rat testes
GILZ inhibits the mTORC2/AKT pathway in BCR-ABL+ cells
The malignant phenotype of chronic myeloid leukemia (CML) is due to the abnormal tyrosine kinase activity of the BCR-ABL oncoprotein, which signals several downstream cell survival pathways, including phosphoinositide 3-kinase/AKT, signal transducer and activator of transcription 5 and extracellular signal-regulated kinase 1/2. In patients with CML, tyrosine kinase inhibitors (TKIs) are used to suppress the BCR-ABL tyrosine kinase, resulting in impressive response rates. However, resistance can occur, especially in acute-phase CML, through various mechanisms. Here, we show that the glucocorticoid-induced leucine zipper protein (GILZ) modulates imatinib and dasatinib resistance and suppresses tumor growth by inactivating the mammalian target of rapamycin complex-2 (mTORC2)/AKT signaling pathway. In mouse and human models, GILZ binds to mTORC2, but not to mTORC1, inhibiting phosphorylation of AKT (at Ser473) and activating FoxO3a-mediated transcription of the pro-apoptotic protein Bim; these results demonstrate that GILZ is a key inhibitor of the mTORC2 pathway. Furthermore, CD34+ stem cells isolated from relapsing CML patients underwent apoptosis and showed inhibition of mTORC2 after incubation with glucocorticoids and imatinib. Our findings provide new mechanistic insights into the role of mTORC2 in BCR-ABL+ cells and indicate that regulation by GILZ may influence TKI sensitivity
Serum lactic dehydrogenase isoenzyme pattern in childhood lymphoblastic leukemia [letter]
Loss of Maternal Allele in a Child with Myelodysplastic Syndrome and Monosomy 7
Monosomy 7 or partial deletion of the long arm of chromosome 7 is frequently described in children with myelodysplastic syndrome and acute myeloblastic leukemia, Parental origin of chromosome 7 in children with sporadic monosomy 7 has been examined very rarely, To investigate if monosomy 7 shows parent-of-origin, we have studied a female child with monosomy 7 and de novo myelodysplastic syndrome by a series of polymorphic polymerase chain reaction markers. We found loss of maternal allele and discussed the results with the previous reports. Am, J, Hematol. 62:49-51, 1999. (C) 1999 Wiley-Liss, Inc
ACUTE LYMPHOBLASTIC-LEUKEMIA IN A CHILD WITH HEMOGLOBINS-S AND Q-IRAN
A 13-year-old girl with acute lymphoblastic leukemia is presented. The peripheral smear showed, in addition to lymphoblasts, marked anisocytosis, poikilocytosis, and polychromasia. In vitro sickling test was positive. Hemoglobin electrophoresis at pH 9.0 on starch gel revealed the presence of hemoglobin A, hemoglobin S, and a band with a mobility of hemoglobin A2. Structural analysis revealed the presence of hemoglobin S and an alphachain variant, hemoglobin Q-Iran. The patient attained remission with the initial therapy administered but a relapse occurred five months later. Our study indicates the need for detailed investigation of leukemia patients in which abnormal hemoglobins are prevalent
Transient Protein S Deficiency With Deep Venous Thrombosis During Salmonella Typhimurium Infection
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