Human leukemic stem cells, like other cancer stem cells, are hypothesized to be rare, capable of incomplete differentiation, and restricted to a phenotype associated with early hematopoietic progenitors or stem cells. However, recent work in other types of tumors has challenged the cancer stem cell model. Using a robust model of xenotransplantation based on NOD/SCID/IL2Rγc-deficient mice, we co...

conclusions collectively, the v. pumilum extracts showed remarkable cytotoxic activity and merit further investigation as anticancer agents. results the ch2cl2 fraction of v. pumilum showed a potent dose-related inhibitory effect on cell viability. the ch2cl2 fraction showed ic50 values of 8.3 and 12.5 µg/ml in the k562 and hl-60 cell lines, respectively. a sub-g1 peak in the flow cytometry his...

Targeting constitutively activated FMS-like tyrosine kinase 3 [(FLT3); FLT3-ITD] with tyrosine kinase inhibitor (TKI) in acute myeloid leukemia (AML) leads to clearance of blasts in the periphery but not in the bone marrow, suggesting a protective effect of the marrow niche on leukemic stem cells. In this study, we examined the effect of stromal niche cells on CD34(+) progenitors from patients ...

Targeting constitutively activated FMS-like tyrosine kinase 3 [(FLT3); FLT3-ITD] with tyrosine kinase inhibitor (TKI) in acute myeloid leukemia (AML) leads to clearance of blasts in the periphery but not in the bone marrow, suggesting a protective effect of the marrow niche on leukemic stem cells. In this study, we examined the effect of stromal niche cells on CD34þ progenitors from patients wi...

The resistance of leukemic stem cells in response to targeted therapies such as tyrosine kinase inhibitors (TKIs) relies on the cooperative activity of multiple signaling pathways and molecules, including TGFβ, AKT, and FOXO transcription factors (TFs). B cell lymphoma 6 (BCL6) is a transcriptional repressor whose translocation or mutation is associated with diffuse large BCL. New data now show...

The host tissue microenvironment influences malignant cell proliferation and metastasis, but little is known about how tumor-induced changes in the microenvironment affect benign cellular ecosystems. Applying dynamic in vivo imaging to a mouse model, we show that leukemic cell growth disrupts normal hematopoietic progenitor cell (HPC) bone marrow niches and creates abnormal microenvironments th...

An understanding of the cell interactions occurring in the leukemic microenvironment and their functional consequences for the different cell players has therapeutic relevance. By co-culturing mesenchymal stem cells (MSC) with the REH acute lymphocytic leukemia (ALL) cell line, we have established an in vitro leukemic niche for the functional evaluation of hematopoietic stem/progenitor cells (H...

Background: Dimethyl Sulfoxide (DMSO) is a solvent most broadly used as a cryopreservative agent. Antitumor effects of DMSO is a recently recognized phenomenon. In this study, cytotoxic effects of DMSO on human monocytes and T leukemic cell lines has been investigated in vitro. Methods: Human leukemic T cells (Molt-4 and Jurkat) and monocytes (U937 and THP1) were cultured in complete RPMI medi...

LL PRESENT FORMS OF THERAPY for acute myelocytic leukemia (AML) injure or destroy normal as well as leukemic cells. The action of anti-metabolic chemotherapeutic drugs is largely directed at disrupting flucleic acid synthesis and, thus, replication of cells. The alkylating agents and whole body radiation are effective in reducing cell production by slowing the generative cycle and directly kill...