Prospective isolation of human erythroid lineage-committed progenitors

Mori, Yasuo; Chen, James Y.; Pluvinage, John V.; Seita, Jun; Weissman, Irving L.

doi:10.1073/pnas.1512076112

Cited by 80 publications

(74 citation statements)

References 52 publications

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“…After that, over the next 25 years we identified nearly each step between HSCs and blood cells both in mice (76,78,134,135) and to a lesser extent in humans (136)(137)(138). These have been tested by in vivo transfers and in vitro assays and provide the basis, described below, of knowing the lineage, the function, the life span, and the gene expression profiles of all of these cell types.…”

Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

“…I did not know then to call the selective gene activation epigenetics and completely missed the ideas that the suppressors of gene expression or cell fates could be what we now call tumor suppressor genes. But when we isolated the HSCs and started to understand their behaviors of self-renewal and differentiation through quantal steps of progenitors of everdecreasing fate potential (76,78,(134)(135)(136)(137)(138), I wondered if the self-renewal programs of normal stem cells could be programs that cancer-propagating cells might require, and therefore whether cancers have evolved their own stem cells. These ideas were with me in the mid-1990s, when Sean Morrison was my graduate student and Michael Clarke was on sabbatical in my lab, and when we were pursuing genes that might be involved in HSC self-renewal (151).…”

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

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How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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“…With ongoing differentiation, at the second stage, CD36, CD71, CD105, CD117, CD173, and CD238 can be observed, whereas CD45 doi: 10.7243/2052-434X-4-3 expression is diminished and HLA-DR is no longer detectable. The third stage is defined by the appearance of CD235a and the disappearance of CD117 [5,6]. In Case 1, neoplastic cells were positive for CD36, but negative for CD235a, exhibiting the early stage after commitment to the erythroid lineage.…”

Section: Discussionmentioning

confidence: 99%

Positive p53 immunostaining and erythroid maturation in two cases of pure erythroid leukemia with extremely complex karyotypes

Mita¹,

Akino²,

Shirato³

et al. 2016

Hematol Leuk

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Pure erythroid leukemia (PEL) is characterized as a neoplastic erythroid hyperproliferation with maturation arrest, showing highly complex karyotypes, prominent clonal evolution, and a very aggressive clinical course. Here, we describe two cases of PEL that evolved from myelodysplastic syndrome (MDS), focusing on the immunophenotypic, cytogenetic, and molecular features of these cases. Case 1: A 77-yearold woman was diagnosed with PEL that evolved from MDS-refractory cytopenia with multilineage dysplasia. Her disease progressed rapidly despite 5 cycles of azacitidine treatment. The bone marrow (BM) aspirate revealed hypercellular marrow with 92.4% erythroid cells, which expressed CD7 and CD36. Case 2: A 43-year-old woman had MDS-refractory anemia for more than 15 years. When her disease progressed rapidly, the BM aspirate revealed hypercellular marrow with 95.4% erythroid cells, which expressed CD235a. There were several significant findings in our cases. First, flow cytometric analysis of BM cells showed different stages of erythroid maturation. Second, cytogenetics revealed extremely complex karyotypes. Finally, immunohistochemistry showed strong nuclear staining for p53 in BM erythroid cells. We suggest that increased p53 protein expression is correlated with complex karyotypes and worse outcomes, indicating PEL with a high degree of malignant behavior.

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“…In aged BM, we observed a prominent increase of h-MEP frequency (Fig 1B), but failed to reproduce a similar increase of m-preMegEs in the murine setting (Fig 1D). This discrepancy could potentially be explained by the possibility that the h-MEP and m-preMegE populations are not fully comparable, particularly as the phenotypical identity and the erythroid versus megakaryocytic potentials at different stages of the human hematopoietic development is debated [44,58,59]. Moreover, changes in levels of platelets and erythrocytes differ in aged humans and mice, with humans showing decreased levels of both red blood cells (RBCs) [60] and platelets [49,61], whereas mice exhibits decreased levels of RBCs [62] but increased levels of platelets [21].…”

Section: Discussionmentioning

confidence: 99%