cisplatin is an effective chemotherapeutics against a wide range of cancers. however, it causes significant nausea and vomiting which limit its usefulness. in the present study, the effects of methanolic root extract of pluchea lanceolata (dc.) c. b. clarke , asteraceae ( mpl ) was investigated against cisplatin-induced nausea using a rat pica model. in rat pica model, rats react to cisplatin (...

Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL-expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self-renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the m...

This study was undertaken to determine whether mouse placental lactogen (mPL)-I, mPL-II, and proliferin (PLF) are expressed by the same population of placental giant cells at midpregnancy. Tissue sections from Day 9 of pregnancy were analyzed by double immunofluorescence staining. Sections were stained for PLF by use of a rhodamine-conjugated second antibody, and for mPL-I or mPL-II by use of a...

The proto-oncogene c-mpl encodes a protein whose sequence shares striking homologies with members of the highly conserved hematopoietin receptor superfamily. This gene had been transduced in a truncated form by the acute leukemogenic murine Myeloproliferative leukemia virus, which exhibits the unique property of inducing factor-independent proliferation and terminal differentiation of a broad s...

Megakaryopoiesis is a 2-step differentiation process, regulated by thrombopoietin (TPO), on binding to its cognate receptor myeloproliferative leukemia (MPL). This receptor associates with intracytoplasmic tyrosine kinases, essentially janus kinase 2 (JAK2), which regulates MPL stability and cell-surface expression, and mediates TPO-induced signal transduction. We demonstrate that JAK2 and MPL ...

The Mpl receptor plays an important role at the level of adult hematopoietic stem cells, but little is known of its function in embryonic and fetal hematopoiesis. We investigated the signals sent by the MPL cytoplasmic domain in fetal liver hematopoietic progenitors and during embryonic stem (ES) cell hematopoietic commitment. Mpl was found to be expressed only from day 6 of ES cell differentia...

After a sublethal exposure to lipopolysaccharide (LPS) or to lipid A, which is that portion of the LPS molecule associated with endotoxicity, a transient period ensues during which a normally responsive individual is rendered hyporesponsive to LPS-induced toxicity. This period has been defined as early-phase endotoxin tolerance. Recently, a nontoxic derivative of lipid A from Salmonella typhimu...

In this study, we analyzed the roles for AML1/RUNX1 in the regulation of the c-mpl promoter. Wild-type AML1 activated the c-mpl promoter through the proximal AML-binding site in luciferase assays using 293T and HeLa cells. In accord with this result, electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrated that AML1 bound to this site. Next, we analyzed the fun...

Thrombopoietin (TPO) acts as a lineage-specific late-acting factor to stimulate megakaryocyte and platelet formation. However, analysis of mice lacking either the cytokine or its receptor, c-Mpl, also revealed deficiencies in progenitor cells of multiple hematopoietic lineages, suggesting that TPO signaling may play an important role in the regulation of the hematopoietic stem cell compartment....

Signal transducer and activator of transcription-5 (STAT5) plays an important role in repopulating activity of hematopoietic stem cells (HSCs). However, the relationship of STAT5 activation with early acting cytokine receptors is not well established. We have directly compared bone marrow (BM) from mice mutant for STAT5a and STAT5b (STAT5ab(-/-)) with that from mice lacking c-Mpl (c-Mpl(-/-)), ...