Leukemia inhibitor factor

The key to expanding a stem cell population is to understand the requirements for proliferation without inducing differentiation. In the case of self-renewal some elements seem to be essential. Examples are the homeotic gene HOXB4, the cytokines FLT-3L (fms-related tyrosine kinase ligand), LIF (leukemia inhibitor factor), interleukin (IL)-3, VEGF (vascular endothelial growth factor), and proteins of the WNT and... 

Savatier, P., Lapillonne, H., van Grunsven, L.A., Rudkin, B.B. and Samarut, J. (1996). Withdrawal of differentiation inhibitory activity/leukemia inhibitory factor up-regulates D-type cyclins and cyclin-dependent kinase inhibitors in mouse embryonic stem cells. Oncogene. Vol. 12 No. 2 pp. 309-322 ISSN 0950-9232... 

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

The proportion of ALL in patients older than age 60 years constitutes between 16% and 31% of all adult leukemias. Treatment of adults largely has followed the conventional chemotherapeutic regimes used in childhood ALL. However, the intensification regimens common in childhood are not suitable for this population because of their associated toxic-ities in older patients. The adverse prognostic factor, the Philadelphia chromosome, occurs in 15% to 30% of adults and thus is more common in the over 60 age group.17 Based on the experience achieved in CML, the use of imatinib, a potent inhibitor of the Ph+-associated BCR-ABL tyrosine kinase, is becoming a common practice for these older adults. Results show that the combination of imatinib with conventional chemotherapy has improved remission rates compared with the use of conventional chemotherapy alone,... 

The inhibitors available for human use, azacitidine and decitabine, have been approved for the treatment of myelodysplastic syndrome (MDS) [98, 99[. MDS summarizes a set of different conditions that affect the maturation of blood cells. It is a group of bone marrow stem cell malignancies that have a pathogenetic overlap with acute myeloid leukemia, show peripheral blood cytopenias and, in more advanced subtypes, varied degrees of maturation arrest [100]. Both drugs are approved for all subtypes of MDS. Response rates are usually around 30%. The question whether the clinical benefit results more from epigenetic effects and re-activation of silenced maturation factors or more from cytotoxic effects on the immature hyperproliferative cells remains open. 

Imatinib (STI571) is an inhibitor of the tyrosine kinase domain of the Bcr-Abl oncoprotein and prevents the phosphorylation of the kinase substrate by ATP. It is indicated for the treatment of chronic myelogenous leukemia (CML), a pluripotent hematopoietic stem cell disorder characterized by the t(9 22) Philadelphia chromosomal translocation. This translocation results in the Bcr-Abl fusion protein, the causative agent in CML, and is present in up to 95% of patients with this disease. This agent inhibits other activated receptor tyrosine kinases for platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF), and c-kit. 

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