Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia

Bernt, Kathrin M.; Armstrong, Scott A.

doi:10.1053/j.seminhematol.2008.09.010

Cited by 46 publications

(31 citation statements)

References 42 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 We found that the expression levels of tmTNF-a were much higher in HSC-enriched leukemia fractions than in nonmalignant cells (P , .001; Figure 1E). However, no significant differences in the levels of tmTNF-a expression could be observed among various subtypes of AL ( Figure 1F-G).…”

Section: Cd7mentioning

confidence: 84%

Transmembrane TNF-α preferentially expressed by leukemia stem cells and blasts is a potent target for antibody therapy

Zhou

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

Section: Cd7mentioning

confidence: 84%

Transmembrane TNF-α preferentially expressed by leukemia stem cells and blasts is a potent target for antibody therapy

Zhou

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

“…CD34 + cells are ideally suited for this analysis, since many translocation events in leukemias and lymphomas are thought to occur within the hematopoietic stem cell population or in early progenitors derived from this population (Bonnet and Dick 1997;Bernt and Armstrong 2009). A set of 74 translocation genes, defined as translocated in at least 10 clinical cases of hematologic malignancies, was selected using the Mitelman Database of Chromosome Aberrations (translocation genes) (Supplemental Table S1).…”

Section: Computational Analysis Of Chromatin Features At Recurrent Brmentioning

confidence: 99%

Histone modifications predispose genome regions to breakage and translocation

et al. 2015

View full text Add to dashboard Cite

Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitizes genome regions to breakage by endonuclease challenge or irradiation and promotes formation of chromosome translocations of endogenous gene loci. Our results demonstrate that histone modifications predispose genome regions to chromosome breakage and translocations.

show abstract

“…22,23 A single clonal population gives rise to the lymphocyte pool, thus the concept of polyclonality versus monoclonality is routinely applied in the diagnostic assessment of lymphoid neoplasm. 24 To assess whether the lymphoid graft derived from AML patients observed in NOD/SCID IL2R␥c null mice was monoclonal or polyclonal in origin, clonal rearrangements of TCR genes, which reflect clonal expansion of T-lymphocytes, were measured in engrafted samples by PCR.…”

Section: Nsg-engrafting Amls Produce a Monoclonal T-cell Lymphoprolifmentioning

confidence: 99%

Identification of T-lymphocytic leukemia–initiating stem cells residing in a small subset of patients with acute myeloid leukemic disease

Risueño

Campbell²,

Dingwall³

et al. 2011

Blood

View full text Add to dashboard Cite

Xenotransplantation of acute myeloid leukemia (AML) into immunodeficient mice has been critical for understanding leukemogenesis in vivo and defining selfrenewing leukemia-initiating cell subfractions (LICs). Although AML-engraftment capacity is considered an inherent property of LICs, substrains of NOD/SCID mice that possess additional deletions such as the IL2R␥c null (NSG) have been described as a more sensitive recipient to assay human LIC function. Using 23 AML-patient samples, 39% demonstrated no detectable engraftment in NOD/SCID and were categorized as AMLs devoid of LICs. However, 33% of AML patients lacking AML-LICs were capable of engrafting NSG recipients, but produced a monoclonal T-cell proliferative disorder similar to T-ALL. These grafts demonstrated selfrenewal capacity as measured by in vivo serial passage and were restricted to CD34-positive fraction, and were defined as LICs. IntroductionOne of the most provocative observations in the field of human cancer biology has been the demonstration that some types of cancer are initiated and sustained by a rare population of cells that possess stem cell characteristics. 1,2 These cells, termed cancer stem cells (CSCs), are best described in human acute myeloid leukemia (AML), representing an aggressive hematopoietic malignancy where an impaired differentiation program results in the accumulation of immature myeloid blasts. 3,4 The identification of a rare self-renewing cell population termed leukemia-initiating cells (LICs) capable of initiating and sustaining growth of human leukemia was based on transplantation of primary AML cells into immunodeficient NOD/SCID mice. 3,4 LICs can be prospectively isolated based on surface-marker expression in the BM and peripheral blood of AML patients. 4,5 Because of their characteristics that include self-renewal and disease initiation, it has been proposed that these cells possess "stem cell-like" properties and are responsible for the occurrence of minimal residual disease (MRD) and related leukemia relapse. 6-9 As such, characterization of the LICs in human leukemia has become an important pursuit for understanding the human leukemogenic process to design new therapies capable of targeting LICs with the overarching goal of eradicating the disease.Although, AML-derived LICs are defined functionally in xenotransplantation models, different strains of immunodeficient mice have been studied to detect human AML-LICs. Initially SCID recipients 3 and subsequently NOD/SCID mice 4 have been widely used to model human leukemia and define the LIC fraction that is restricted to the CD34 ϩ population. 3,4 Further modification of the NOD/SCID, especially the absence of ␤2 microglobulin in NOD/SCID ␤2 Ϫ/Ϫ mice lacking the expression of MHC class I, diminishes host innate response and permits enhanced human leukemia engraftment. 10 More recently, IL2R␥c (CD132) deficient NOD/SCID mice have impaired signaling through multiple cytokine receptors, resulting in blocked NK-cell development and severely decreased immune response, ...

show abstract

Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia

Cited by 46 publications

References 42 publications

Transmembrane TNF-α preferentially expressed by leukemia stem cells and blasts is a potent target for antibody therapy

Transmembrane TNF-α preferentially expressed by leukemia stem cells and blasts is a potent target for antibody therapy

Histone modifications predispose genome regions to breakage and translocation

Identification of T-lymphocytic leukemia–initiating stem cells residing in a small subset of patients with acute myeloid leukemic disease

Contact Info

Product

Resources

About