The stem cell in the pathogenesis and treatment of myelogenous leukemia: a perspective

Ma, Lichtman

doi:10.1038/sj.leu.2402247

Cited by 17 publications

(9 citation statements)

References 15 publications

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“…Although careful studies using microscopic analysis pointed to the idea of a common stem cell for all blood lineages, 31 equally robust was the view that independent stem cells existed for each major blood lineage, which was promulgated by textbooks from the 1940s. 32 The experimental finding by Till and McCulloch that the "regeneration nodules" on the spleen of lethally irradiated mice (termed CFU-spleen [CFU-S]) 33 transplanted with BM cells were clonal (based on X-ray induced chromosomal lineage tracking 34 ) and contained multiple blood lineages proved that the hematopoietic system derives from a multipotent HSC rather than from a series of lineage-specific stem cells. With a clonal, quantitative, and functional assay in hand, in short order they established all of the major stem cell principles under which we continue to operate today: HSCs have a high capacity for self-renewal, proliferation, and multipotential differentiation.…”

Section: Identification Of Normal Hscs In the Mousementioning

confidence: 99%

Stem cell concepts renew cancer research

Dick

2008

Blood

926

759

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Although uncontrolled proliferation is a distinguishing property of a tumor as a whole, the individual cells that make up the tumor exhibit considerable variation in many properties, including morphology, proliferation kinetics, and the ability to initiate tumor growth in transplant assays. Understanding the molecular and cellular basis of this heterogeneity has important implications in the design of therapeutic strategies. The mechanistic basis of tumor heterogeneity has been uncertain; however, there is now strong evidence that cancer is a cellular hierar- IntroductionTumors from different patients, whether leukemic or solid, exhibit significant heterogeneity in terms of morphology, cell surface markers, genetic lesions, cell proliferation kinetics, and response to therapy. Heterogeneity of all these features is also seen within an individual tumor that is clonal (ie, initiated from a single cell). Although individual cells of a tumor all share common genetic aberrations reflective of their clonal origin, single-cell analysis has shown the existence of variation in genetic and epigenetic abnormalities between different cells or locations within a tumor. The cellular and molecular basis for this heterogeneity represents a fundamental problem that has interested cancer researchers for many decades. One possible explanation is that all tumor cells could be biologically equivalent and heterogeneity derives from extrinsic or intrinsic influences that result in random or stochastic responses. Alternatively, it is possible that the tumor is a caricature of normal tissue development and retains hierarchical organization with (cancer) stem cells at the apex. 1 This review will focus on 50 years of hematology research that played a role in garnering evidence to support the hierarchy model.There is mounting evidence from cell purification studies that a subset of cells, termed cancer stem cells (CSCs), or cancerinitiating cells, that are distinct from the bulk of the tumor are responsible for long-term maintenance of tumor growth in several cancers. 2 Evidence is strongest for the acute leukemias, although recent studies have identified the existence of CSCs in an increasingly longer list of solid tumors, including brain, breast, and colon. 3 This conceptual shift has important implications, not only for researchers seeking to understand mechanisms of tumor initiation and progression but also for developing and evaluating effective anticancer therapies. Although the clinical relevance of CSCs beyond experimental models is still lacking, the high frequency of relapse after conventional cytotoxic chemotherapies predicts that CSCs survive standard treatments. Many papers, reviews, and funding bodies are making strong predictions that targeting CSCs more effectively will lead to improved patient outcomes. Indeed, there has been almost breathless excitement that this "new" field of CSC biology will solve the stubbornly high relapse rates that continue to exist for many cancers. However, stem cell concepts and how they apply...

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Section: Identification Of Normal Hscs In the Mousementioning

confidence: 99%

Stem cell concepts renew cancer research

Dick

2008

Blood

926

759

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“…The cell type which should be considered as anMDS "stem" cell is yet to be disclosed. Whether it is a multipotential stem cell or progenitor cell remains controversial [6,[35][36][37][38][39]. The 'mutator stem cell' theory describes that acquired mutations at a critical stage in hematopoiesis act as the basis for additional genetic events during the onset of MDS [36].…”

Section: The Occurrence Of Cytogenetic Abnormalities In Mdshscsmentioning

confidence: 99%

“…Hence hematopoietic stem/ progenitor compartment has drawn the central attention of MDS research. MDS is still considered as a true stem cell disorder despite both supportive and oppose evidence for the idea that it may more commonly occur in multipotent myeloid lineages [6,[35][36][37][38][39].…”

Section: The Occurrence Of Cytogenetic Abnormalities In Mdshscsmentioning

confidence: 99%

“…Cytogenetic analyses have identified various clonal chromosomal abnormalities in the cells of hematopoietic hierarchy including hematopoietic stem/progenitors as well as in the myeloid and lymphoid lineages of blood cells [35][36][37][38][39][40][41]. The common recurring cytogenetic abnormalities in MDS include del(5q), -7/del(7q), -8,-18/del (18q), del (20q),-5,-Y,-17/del (17p) including isochromosome (17q), -21, inv/t(3q), -13/del (13q), -1/del (1q), -21, -11, del (12p), t(5q), del (11q), and t(7q) [1,2,[35][36][37][38][39][40][41][42][43].…”

Section: The Occurrence Of Cytogenetic Abnormalities In Mdshscsmentioning

confidence: 99%

“…The common recurring cytogenetic abnormalities in MDS include del(5q), -7/del(7q), -8,-18/del (18q), del (20q),-5,-Y,-17/del (17p) including isochromosome (17q), -21, inv/t(3q), -13/del (13q), -1/del (1q), -21, -11, del (12p), t(5q), del (11q), and t(7q) [1,2,[35][36][37][38][39][40][41][42][43]. The initiator hematopoietic cell with cytogenetic abnormalities in the hierarchy of hematopoiesis is yet to be identified.…”

Section: The Occurrence Of Cytogenetic Abnormalities In Mdshscsmentioning

confidence: 99%

See 2 more Smart Citations

Development of Cytogenetic Abnormalities in Myelodysplastic Syndromes

WMMS¹,

AJIS²

2016

J Mol Genet Med

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Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis resulting in cellular dysplasia and peripheral cytopenias. Research into MDS have found that both hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) in the nurturing niche of HSCs are genetically altered in MDS. In this review we present the existing views on the origin of cytogenetic abnormalities in HSC and MSC compartments in MDS. Based on the available data, we speculate that the origin of the chromosomal aberrations of the hematopoietic compartment occurs at the hematopoietic stem/ progenitor level. The genetic aberrations in MSC compartment appears to initiate independently from their hematopoietic counterparts. Whether the genetic events in both HSC and MSC compartments which lead to MDS occur simultaneously or at different time points in the disease development need to be determined in future.

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Acute Myeloid Leukemias

Valli¹

2007

Veterinary Comparative Hematopathology

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The stem cell in the pathogenesis and treatment of myelogenous leukemia: a perspective

Cited by 17 publications

References 15 publications

Stem cell concepts renew cancer research

Stem cell concepts renew cancer research

Development of Cytogenetic Abnormalities in Myelodysplastic Syndromes

Acute Myeloid Leukemias

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