Human megakaryocytic progenitor cells

Kanz, Lothar; Löhr, G. W.; Fauser, AA

doi:10.1007/bf01745383

Cited by 12 publications

(4 citation statements)

References 102 publications

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“…The 11E4B7.6 (KC16) mAb conjugated FITC was specific for glycophorin A, a major transmembrane sialoglycoprotein expressed on red blood cells and erythroid precursors. The P2 mAb conjugated to PE was specific for CD41 or the GPIIb component of the GPIIb/IIIa complex present on platelets and early promegakaryoblasts (Kanz et al, 1987). The 679.1 Mc7 monoclonal antibodies served as isotype controls (IgG 1 -FITC and IgG 1 -PE) possessing irrelevant specificity.…”

Section: Methodsmentioning

confidence: 99%

The Catalytic DNA Topoisomerase II Inhibitor Dexrazoxane (ICRF-187) Induces Differentiation and Apoptosis in Human Leukemia K562 Cells

et al. 2001

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The bisdioxopiperazines ICRF-187 (dexrazoxane), ICRF-193, and ICRF-154 are catalytic noncleavable complex-forming inhibitors of DNA topoisomerase II that do not produce protein-linked DNA strand breaks. In this study, we showed that bisdioxopiperazines induced erythroid differentiation, inhibited human leukemia K562 cell growth, and caused a slow induction of apoptosis. Dexrazoxane treatment caused DNA endoreduplication resulting in large highly polyploid cells. This result suggested the lack of a DNA topoisomerase II activity-based cell cycle checkpoint. The percentage of K562 cells that became apoptotic was much larger than the percentage of cells that stained for hemoglobin, suggesting that prior differentiation was not required for induction of apoptosis. Use of the Bcr-Abl tyrosine kinase inhibitor STI-571 resulted in a reduction in Bcl-xL levels and potentiation of dexrazoxane-induced apoptosis related to an earlier onset and more extensive cleavage of caspase-3. These results indicated that dexrazoxane-induced apoptosis is associated with a caspase-3 activation/cleavage pathway. In addition, these results were consistent with the antiapoptotic signaling function of Bcr-Abl to regulate expression of Bcl-xL. The ability of dexrazoxane to induce differentiation and apoptosis suggests that bisdioxopiperazines may be useful in treating some types of leukemia.

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Section: Methodsmentioning

confidence: 99%

The Catalytic DNA Topoisomerase II Inhibitor Dexrazoxane (ICRF-187) Induces Differentiation and Apoptosis in Human Leukemia K562 Cells

et al. 2001

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“…Along the developmental cascade, a key separation in progenitor lineages occurs between the major lymphoid progenitors along with granulocytic progenitors versus the major erythromegakaryocytic progenitor cells [92, 77, 78, 93]. Common myeloid progenitor cells (CMP) give rise to megakaryocyte-erythroid progenitor (MEP) cells that are in turn delineated into megakaryopoietic progenitors (MKP) [94]. Ultimately, MKP undergo a complicated maturation process from immature to mature megakaryocytes before finally generating platelets [92, 77, 69, 95, 93].…”

Section: Megakaryocyte and Platelet Biologymentioning

confidence: 99%

Platelets and cancer: a casual or causal relationship: revisited

Menter

Tucker

Kopetz

et al. 2014

Cancer Metastasis Rev

279

256

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Human platelets arise as subcellular fragments of megakaryocytes in bone marrow. The physiologic demand, presence of disease such as cancer, or drug effects can regulate the production circulating platelets. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. The most critical biological platelet response is serving as “First Responders” during the wounding process. The exposure of extracellular matrix proteins and intracellular components occurs after wounding. Numerous platelet receptors recognize matrix proteins that trigger platelet activation, adhesion, aggregation, and stabilization. Once activated, platelets change shape and degranulate to release growth factors and bioactive lipids into the blood stream. This cyclic process recruits and aggregates platelets along with thrombogenesis. This process facilitates wound closure or can recognize circulating pathologic bodies. Cancer cell entry into the blood stream triggers platelet-mediated recognition and is amplified by cell surface receptors, cellular products, extracellular factors, and immune cells. In some cases, these interactions suppress immune recognition and elimination of cancer cells or promote arrest at the endothelium, or entrapment in the microvasculature, and survival. This supports survival and spread of cancer cells and the establishment of secondary lesions to serve as important targets for prevention and therapy.

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“…The CD235a fluorescein isothiocyanate (FITC)-conjugated mAb was specific for glycophorin A, a major transmembrane sialoglycoprotein expressed on red blood cells and erythroid precursors. The CD41 mAb conjugated to phycoerythrin (PE) was specific for the GPIIb component of the GPIIb/IIIa complex present on platelets and early promegakaryoblasts [45], and CD42 FITC-conjugated mAb was specific for glycoprotein Ib, a component of the GPIb-V-IX complex on platelets. Each mAb was added in turn to approximately 5×10 5 cells in 150 µl of RPMI/fetal bovine serum, lightly vortexed, and then incubated on ice for 45 min.…”

Section: Methodsmentioning

confidence: 99%

A Natural-Like Synthetic Small Molecule Impairs Bcr-Abl Signaling Cascades and Induces Megakaryocyte Differentiation in Erythroleukemia Cells

et al. 2013

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Over the past years, we synthesized a series of new molecules that are hybrids of spirocyclic ketones as complexity-bearing cores with bi- and ter-phenyls as privileged fragments. Some of these newly-shaped small molecules showed antiproliferative, pro-apoptotic and differentiating activity in leukemia cell lines. In the present study, to investigate more in depth the mechanisms of action of these molecules, the protein expression profiles of K562 cells treated with or without the compounds IND_S1, MEL_T1, IND_S7 and MEL_S3 were analyzed using two-dimensional gel electrophoresis coupled with mass spectrometry. Proteome comparisons revealed several differentially expressed proteins, mainly related to cellular metabolism, chaperone activity, cytoskeletal organization and RNA biogenesis. The major results were validated by Western blot and qPCR. To attempt integrating findings into a cellular signaling context, proteomic data were explored using MetaCore. Network analysis highlighted relevant relationships between the identified proteins and additional potential effectors. Notably, qPCR validation of central hubs showed that the compound MEL_S3 induced high mRNA levels of the transcriptional factors EGR1 and HNF4-alpha; the latter to our knowledge is reported here for the first time to be present in K562 cells. Consistently with the known EGR1 involvement in the regulation of differentiation along megakaryocyte lineage, MEL_S3-treated leukemia cells showed a marked expression of glycoprotein IIb/IIIa (CD41) and glycoprotein Ib (CD42), two important cell markers in megakaryocytic differentiation, together with morphological aspects of megakaryoblasts and megakaryocytes.

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Human megakaryocytic progenitor cells

Cited by 12 publications

References 102 publications

The Catalytic DNA Topoisomerase II Inhibitor Dexrazoxane (ICRF-187) Induces Differentiation and Apoptosis in Human Leukemia K562 Cells

The Catalytic DNA Topoisomerase II Inhibitor Dexrazoxane (ICRF-187) Induces Differentiation and Apoptosis in Human Leukemia K562 Cells

Platelets and cancer: a casual or causal relationship: revisited

A Natural-Like Synthetic Small Molecule Impairs Bcr-Abl Signaling Cascades and Induces Megakaryocyte Differentiation in Erythroleukemia Cells

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