Skip to main content

Regenerative Medicine (2003) / Chapter Skim
Currently Skimming:

6 Normal and leukemic hematopoiesis: Are leukemias a stem cell disorder or a reacquisition of stem cell characteristics?
Pages 26-33

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 26...
... that undergo an aberrant and poorly regulated process of organogenesis analogous to that of normal hematopoietic stem cells. A hallmark of all cancers is the capacity for unlimited self-renewal, which is also a defining characteristic of normal stem cells.
Read the entire page →
From page 27...
... and HSCs have long been considered to be a resting cell population, with only a few stem cells contributing to steady-state hematopoiesis. In fact, recent studies have shown that in young adult mice ~8-10% of LT-HSCs randomly enter the cell cycle per day, with all HSCs entering the cell cycle in 1-3 months (24, 25)
Read the entire page →
From page 28...
... Furthermore, retroviral transduction of constitutively activated I3-catenin into HSCs leads to their expansion in vitro, and retroviral transduction of the Wnt pathway inhibitor axin leads to inhibition of HSC proliferation, increased HSC death in vitro, and reduced reconstitution in vivo (56~. Soluble partially purified Wnt proteins obtained from conditioned supernatants have also been shown to influence the proliferation of CD34+ hematopoietic progenitors isolated from mouse fetal livers and human bone marrow (57, 58~.
Read the entire page →
From page 29...
... A given leukemia can be viewed as a newly formed abnormal hematopoietic tissue initiated by a few LSCs that undergo an aberrant and poorly regulated process of organogenesis analogous to that of normal HSCs. LSCs can either be HSCs, which have become leukemic as the result of accumulated mutations, or more restricted progenitors, which have reacquired the stem cell capability of self-renewal.
Read the entire page →
From page 30...
... The failure of PML/RARor to cause leukemia when expressed from the CDllb promoter during late myeloid differentiation, and the differences in the phenotypes resulting from hCG- and hMRP8-directed PML/RARor expression most likely reflect the difference in the expression profile given by these two promoters and reveal the importance of the developmental stage of the cells targeted by the transgene promoter for the leukemogenic effect of the leukemic-associated fusion gene (83~. A recent study using retroviral transduction of highly purified HSCs, CMPs, and GMPs also has shown that the potent leukemic-fusion gene MLL-ENL, which results from the t(11,19)
Read the entire page →
From page 31...
... Although leukemias are heterogeneous in terms of phenotypes, there are general mechanisms underlying leukemic transformation such as increased cell survival, increased proliferation capacity, increased self-renewal capacity, genomic instability, and prevention of differentiation. Examples of such deregulated mechanisms and/or signaling pathways that have been found in various types of leukemias are indicated.
Read the entire page →
From page 32...
... If phenotypic markers were available that facilitated the rapid identification of LSCs within bone marrow or peripheral blood via flow cytometry, then clinicians could more adequately assess the disease status and respond with the most appropriate treatment, including chemotherapy, blood or bone marrow transplant, biologic response modifier therapy, or molecularly targeted therapies. LSC phenotypic identification may also facilitate early diagnosis of disease relapse postchemotherapy or hematopoietic cell transplants and could allow the elimination of LSC contamination from hematopoietic cell transplants with cell sorting technologies.
Read the entire page →
From page 33...
... 40. Richman, C
Read the entire page →

Key Terms

  • bone marrow
  • leukemic cells
  • stem cell
  • committed progenitors
  • cell cycle

  • fusion proteins
  • cell death
  • accumulated mutations
  • myeloid leukemias
  • normal stem

  • hematopoietic stem
  • hematopoietic cells
  • fusion protein
  • additional mutations
  • programmed cell

  • leukemic transformation
  • myeloid cells
  • fusion gene
  • myeloid progenitors
  • restricted progenitors

  • progenitor cells
  • signaling pathways
  • transgenic mice
  • normal hscs
  • hematopoietic tissue

  • blood cells
  • differentiation potential
  • organogenesis analogous
  • increased proliferation
  • cell populations


    • This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
    More information on Chapter Skim is available.