Emerging evidence suggests cancer stem cells sustain neoplasms; however, little is understood of the normal cell initially targeted and the resultant cancer stem cells. We show here, by tracking individual human leukemia stem cells (LSCs) in nonobese diabetic-severe combined immunodeficiency mice serially transplanted with acute myeloid leukemia cells, that LSCs are not functionally homogeneous but, like the normal hematopoietic stem cell (HSC) compartment, comprise distinct hierarchically arranged LSC classes. Distinct LSC fates derived from heterogeneous self-renewal potential. Some LSCs emerged only in recipients of serial transplantation, indicating they divided rarely and underwent self-renewal rather than commitment after cell division within primary recipients. Heterogeneity in LSC self-renewal potential supports the hypothesis that they derive from normal HSCs. Furthermore, normal developmental processes are not completely abolished during leukemogenesis. The existence of multiple stem cell classes shows the need for LSC-targeted therapies.
Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy
Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in nonobese diabetic-scid/scid mice
Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors
Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias
Retroviral marking of acute myelogenous leukemia progenitors that initiate long-term culture and growth in immunodeficient mice
Identification of variables determining the engraftment potential of human acute myeloid leukemia in the immunodeficient NOD/SCID human chimera model
Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences
Transduction of human CD34+ CD38- bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors
The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells
Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells.
Detection, isolation, and stimulation of quiescent primitive leukemic progenitor cells from patients with acute myeloid leukemia (AML).
Lentivector-mediated clonal tracking reveals intrinsic heterogeneity in the human hematopoietic stem cell compartment and culture-induced stem cell impairment.
Differential role of epigenetic modulators in malignant and normal stem cells: a novel tool in preclinical in vitro toxicology and clinical therapy
Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells
Assessment of the downstream portion of the mitochondrial pathway of caspase activation in patients with acute myeloid leukemia
Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications
Highly enriched CD133(+)CD44(+) stem-like cells with CD133(+)CD44(high) metastatic subset in HCT116 colon cancer cells
Stochastic acquisition of a stem cell-like state and drug tolerance in leukemia cells stressed by radiation
Ovarian tumor initiating cell populations persist following paclitaxel and carboplatin chemotherapy treatment in vivo
Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment
PML-RARalpha initiates leukemia by conferring properties of self-renewal to committed promyelocytic progenitors
Absence of IL-12Rβ2 in CD33(+)CD38(+) pediatric acute myeloid leukemia cells favours progression in NOD/SCID/IL2RγC-deficient mice
The role of minor subpopulations within the leukemic blast compartment of AML patients at initial diagnosis in the development of relapse
Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations
Lentiviral marking of patient-derived acute lymphoblastic leukaemic cells allows in vivo tracking of disease progression
Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma
Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region
AML: Role of LSD1 by CRISPR (Keystone)
Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.
Blood And Marrow Transplantation
The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.