Identification and biology of CML stem cells

Hiromi Iwasaki, Koichi Akashi

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Chronic myeloid leukemia (CML) is a typical model to study cancer stem cell biology. CML stem cells reside in the CD34+CD38 fraction coexisting with normal hematopoietic stem cells (HSCs). By acquisition of BCR-ABL, an oncogenic fusion transcript encoding a constitutively active tyrosine kinase, HSCs become CML stem cells and progressively outgrow normal HSCs at the stem cell niche. The majority of CML stem cells is dormant but expands their clones mainly at the myeloid progenitor stage. Therefore, the effective target of tyrosine kinase inhibitor (TKI) is proliferating CML progenitors, and a fraction of CML stem cells persist after long-term TKI treatment. Thus, CML stem cells are heterogeneous, containing a population not addicted to the BCR-ABL kinase signaling. Importantly, those residual CML stem cells express BCR-ABL at a very low level. We hypothesize that the acquisition of BCR-ABL is not sufficient for HSC to become CML stem cells, because BCR-ABL is sometimes detectable in healthy individuals. Such BCR-ABL-expressing HSCs might be pre-CML stem cells, and additional events upregulating BCR-ABL expression might be required for formation of CML stem cells.

Original languageEnglish
Title of host publicationMolecular Pathogenesis and Treatment of Chronic Myelogenous Leukemia
PublisherSpringer Japan
Pages1-10
Number of pages10
ISBN (Electronic)9784431557142
ISBN (Print)9784431557135
DOIs
Publication statusPublished - Jan 1 2015

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Myeloid Progenitor Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hematopoietic Stem Cells
Protein-Tyrosine Kinases
Stem Cell Niche
Neoplastic Stem Cells
Cell Biology
Phosphotransferases
Clone Cells

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Iwasaki, H., & Akashi, K. (2015). Identification and biology of CML stem cells. In Molecular Pathogenesis and Treatment of Chronic Myelogenous Leukemia (pp. 1-10). Springer Japan. https://doi.org/10.1007/978-4-431-55714-2_1

Identification and biology of CML stem cells. / Iwasaki, Hiromi; Akashi, Koichi.

Molecular Pathogenesis and Treatment of Chronic Myelogenous Leukemia. Springer Japan, 2015. p. 1-10.

Research output: Chapter in Book/Report/Conference proceedingChapter

Iwasaki, H & Akashi, K 2015, Identification and biology of CML stem cells. in Molecular Pathogenesis and Treatment of Chronic Myelogenous Leukemia. Springer Japan, pp. 1-10. https://doi.org/10.1007/978-4-431-55714-2_1
Iwasaki H, Akashi K. Identification and biology of CML stem cells. In Molecular Pathogenesis and Treatment of Chronic Myelogenous Leukemia. Springer Japan. 2015. p. 1-10 https://doi.org/10.1007/978-4-431-55714-2_1
Iwasaki, Hiromi ; Akashi, Koichi. / Identification and biology of CML stem cells. Molecular Pathogenesis and Treatment of Chronic Myelogenous Leukemia. Springer Japan, 2015. pp. 1-10
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