Over the last 40 years the hematopoietic system has provided many of the important paradigms that guide our understanding of stem cell function. Much of our knowledge of the regulation of the hematopoietic system is derived from experiments in the mouse; these studies have involved identification of various classes of progenitor cells, growth factors that stimulate growth and differentiation, a...

The cancer stem cell hypothesis has evolved to one of the most important paradigms in biomedical research. During recent years evidence has been accumulating for the existence of stem cell-like populations in different cancers, especially in leukemias. In the current work we propose a mathematical model of cancer stem cell dynamics in leukemias. We apply the model to compare cellular properties...

Polycomb proteins are classical regulators of stem cell self-renewal and cell lineage commitment and are frequently deregulated in cancer. Here, we find that the non-canonical PRC1.1 complex, as identified by mass-spectrometry-based proteomics, is critically important for human leukemic stem cells. Downmodulation of PRC1.1 complex members, like the DNA-binding subunit KDM2B, strongly reduces ce...

It has been proposed that inhibitors of an oncogene's effects on multipotent hematopoietic progenitor cell differentiation may change the properties of the leukemic stem cells and complement the clinical use of cytotoxic drugs. Using zebrafish, we developed a robust in vivo hematopoietic differentiation assay that reflects the activity of the oncogene AML1-ETO. Screening for modifiers of AML1-E...

Nowadays, more than 90% of patients affected by chronic myeloid leukemia (CML) survive with a good quality of life, thanks to the clinical efficacy of tyrosine kinase inhibitors (TKIs). Nevertheless, point mutations of the ABL1 pocket occurring during treatment may reduce binding of TKIs, being responsible of about 20% of cases of resistance among CML patients. In addition, the presence of leuk...

background and objective: vascular endothelial growth factor (vegf) is a cytokine which is overexpressed in many malignant cancers including leukemia. vegf plays an important role in tumor invasion and metastasis. determination of the pattern of vegf expression in human leukemic cell lines could be useful not only in screening of new antileukemic agents but also to study the mechanism of their ...

Currently lymphoma is mainly treated with combination chemotherapy, hematopoietic stem cell transplantation, immunotherapy, and new targeted therapy, but treatment-related drug resistance, recurrence, extranodal central infiltration, leukemic transformation are still clinical problems that need to be solved urgently. Studies have shown cytokines expressed varying degrees in patients, which sign...

The anti-apoptotic proteins Bcl-XL and Bcl-2 are abundantly expressed in hematopoietic stem cells and/or progenitor cells. Furthermore, leukemic cells expressing these proteins are enriched in minimal residual disease cell populations. This prompted us to test the BH3-mimetic compound ABT-737 for its ability to eradicate putative leukemic stem cells. ABT-737 demonstrated potent cytotoxic effect...

Acute Myeloid Leukaemia (AML) is a phenotypically and genetically heterogenous blood cancer characterised by very poor prognosis, with disease relapse being the primary cause of treatment failure. AML heterogeneity arise from different genetic non-genetic sources, including its proposed hierarchical structure, leukemic stem cells (LSCs) progenitors giving origin to variety more mature subsets. ...