New Strategies in the Treatment of Acute Myelogenous Leukemia (AML): In Vitro Culture of AML Cells—The Present Use in Experimental Studies and the Possible Importance for Future Therapeutic Approaches

Abstract

In vitro studies of cultured native acute myelogenous leukemia (AML) blasts and cell lines have contributed significantly to our present knowledge about the pathogenesis of AML. In the present article we review different techniques for preparation and in vitro culture of AML blasts. Well-characterized serum-free in vitro conditions can now be used in experimental studies of AML, and this makes comparisons between different studies easier. We also describe assays for characterization of AML progenitor subsets (i.e., suspension cultures, colony assays, long-term in vitro culture, xenotransplantation in immunocompromised mice), and we discuss the possible use of AML cell lines as experimental models in AML. Furthermore, clinical studies suggest that the in vitro growth characteristics of AML blasts assayed by short-term culture of the total native populations can be used as a predictor of prognosis after intensive chemotherapy. These in vitro assays may therefore be used for more accurate identification of prognostic parameters and thereby form a basis for the development of simplified laboratory techniques suitable for routine evaluation of patients undergoing risk-adapted therapy. However, it will be equally important to further evaluate the clinical relevance of assays for primitive AML progenitors, and to develop simplified methods that can be used to characterize these progenitor subsets in the routine clinical evaluation.

The proteasome inhibitors bortezomib and PR‐171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells

“…The proapoptotic properties of the proteasome inhibitors seen in assays of a few days duration mainly reflect the characteristics of the more mature majority of leukaemia cells, whereas the proliferation in suspension cultures reflects an enrichment of more immature clonogenic cells (Bruserud et al, 2001). We therefore investigated the effect of bortezomib and PR-171 for these minor subsets of AML cells: (i) the clonogenic cells that represent a small minority of the AML cell population and are regarded as less mature; and (ii) the CD34 + AML cell subset that seems to include the leukaemic stem cells (i.e.…”

“…We therefore investigated the effect of bortezomib and PR-171 for these minor subsets of AML cells: (i) the clonogenic cells that represent a small minority of the AML cell population and are regarded as less mature; and (ii) the CD34 + AML cell subset that seems to include the leukaemic stem cells (i.e. those cells responsible for long-term in vitro proliferation and repopulation in xenografted immunocompromised mice) for most patients (Bruserud et al, 2001;Bonnet, 2005;Guo et al, 2006). Our results demonstrated that bortezomib and PR-171 have antiproliferative effects on the more immature subsets within the hierarchically organised AML cell populations.…”

Animal models of acute myelogenous leukaemia – development, application and future perspectives

“…Expansion of AML in vitro culture systems are generally limited to immortalised cell lines, shortterm culture of primary explants and assays on clinical samples. [280][281][282] These in vitro models fail to engage decisive issues such as cellular/environmental interactions, invasiveness and angiogenesis in AML, thus necessitating development of a relevant xenotransplantation animal model.…”

Serum levels of angiogenin, basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute myelogenous leukemia

“…AML blasts were derived from 59 patients. The cells were prepared from peripheral blood samples by density gradient separation (Ficoll-Hypaque with specific density 1.077; NyCoMed, Oslo, Norway) as described in detail previously, 51 and the percentage of leukemic cells in this population exceeded 95%.…”