Hematopoietic Stem Cells, Regenerative Medicine, and Leukemogenesis

Weissman, Irving

doi:10.1002/9781118416426.ch4

Cited by 3 publications

(2 citation statements)

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“…The stem cell niche may be important for engraftment and recovery of hematopoietic activity after HSCT. [46][47][48][49] We observed that independence of platelet transfusion support was attained more rapidly, as compared to independence of RBC transfusions. Perhaps this is related to differences in the growth conditions permissive for lineage-committed megakaryocyte progenitors and production of mature platelets, as compared to erythroid progenitors and development of fully differentiated RBC.…”

Section: Discussionmentioning

confidence: 87%

Transfusion support for matched sibling allogeneic hematopoietic stem cell transplantation (1993–2010): factors that predict intensity and time to transfusion independence

et al. 2018

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Background: Patients undergoing allogeneic hematopoietic stem cell transplant (HCT) require variable, often extensive transfusion support. Identification of factors that predict urgent, intensive, or special needs should improve management of these patients. Study Design and Methods: This is a retrospective study of red blood cell (RBC) and platelet transfusion support provided for sequential matched sibling donor (MSD) allogeneic transplants conducted at the Clinical Center, NIH, from 1993-2010. Factors potentially important for predicting quantity of RBC and platelet transfusions, and time to transfusion independence through Day 200 post-HCT were evaluated. Results: Subjects (n=800) received 10,591 RBC and 10,199 platelet transfusions. Multivariable analysis demonstrated that need for RBC pretransplant, CD34+ dose, transplant year, diagnostic category, and ABO match were significantly independently associated with quantity of RBC transfusions Days 0-30. Only pretransplant need for RBC, CD34+ dose and transplant year had significance during Days 0-100. Similar analyses for quantity of platelet transfusions demonstrated that for both Days 0-30 and 0-100, significant factors were need for platelet support pretransplant, CD34+ dose, transplant year, and transplant regimen. Of note, long term, during Days 101-200, only CD34+ dose remained significant for quantity of RBC and of platelet transfusions. Analysis of time to transfusion independence demonstrated that patients with ABO major mismatches required longer to achieve freedom from RBC transfusion support compared to identical matches or those with minor mismatches. Conclusion: Patient-specific factors including CD34+ dose and ABO match of the graft should be given particular consideration by transfusion services when planning support of patients receiving allogeneic HCT.

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Section: Discussionmentioning

confidence: 87%

Transfusion support for matched sibling allogeneic hematopoietic stem cell transplantation (1993–2010): factors that predict intensity and time to transfusion independence

et al. 2018

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“…Abbreviations: CLP, common lymphoid progenitor; CMP, common myeloid progenitor; EP, erythroid progenitor; GMP, granulocyte/macrophage progenitor; GP, granulocyte progenitor; MacP, macrophage progenitor; MEP, megakaryocyte/erythroid progenitor; MkP, megakaryocyte progenitor; Pro-B, B lymphocyte progenitor; Pro-DC, dendritic cell progenitor; Pro-NK, natural killer cell progenitor; Pro-T, T lymphocyte progenitor. Reproduced with permission from Wiley(139).…”

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confidence: 99%

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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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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.

show abstract

Hematopoietic Stem Cells, Regenerative Medicine, and Leukemogenesis

Cited by 3 publications

References 446 publications

Transfusion support for matched sibling allogeneic hematopoietic stem cell transplantation (1993–2010): factors that predict intensity and time to transfusion independence

Transfusion support for matched sibling allogeneic hematopoietic stem cell transplantation (1993–2010): factors that predict intensity and time to transfusion independence

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How One Thing Led to Another

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