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Leukemias are a group of hematologic malignancies that originate in the bone marrow (BM) in an acute or chronic manner, leading to an abnormal expansion of white blood cells due to abnormalities in lymphoid or myeloid progenitors. Leukemic stem cells (LSCs), a rare subpopulation, originate from cancer stem cells (CSCs) and represent a major contributor to the relapse of leukemia. These cells possess the characteristics of stem cells, including self-renewal, quiescence, and resistance to chemotherapy. They frequently reside in the CD34+CD38− compartment. Certain surface markers, such as CD123, CD44, CD47, TIM-3, CLL-1, and CD96, can identify LSCs and differentiate them from healthy hematopoietic stem cells (HSCs). These markers could also serve as therapeutic targets. The abnormal activation of important developmental and oncogenic pathways, including Wingless-related integration site (WNT)/β-catenin, Hedgehog, Notch, PI3K/Protein Kinase B (AKT)/mTOR, and NF-κB, controls the survival and maintenance of LSCs. This is frequently done in conjunction with epigenetic changes and metabolic rewiring. These pathways, in addition to other pathways such as Transforming growth factor (TGF)-β, TLR and p53, are implicated in the biology of LSCs and contribute to the escape of LSCs from immune cells as well as their persistence during remission. Recent studies have advanced our understanding of LSC biology and the development of several drugs that can target LSCs based on specific phenotypic and molecular characteristics. Despite these developments, challenges including immune evasion, phenotypic plasticity, and bone marrow protection still exist. This chapter will focus on a deeper understanding of the unique cellular and molecular LSC signatures and their roles in poor prognosis and disease relapse, as well as on the potential drugs that target either LSC markers or certain pathways in LSCs.

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Phenotypic Signature of Leukemic Stem Cells and Their Signaling Pathways for Potential Targeting Strategies

  • 章节

  • 发表日期：

    2026年

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  • Mohamed L. Salem,
  • Samar Sakr,
  • Samar Salman,
  • Eman Elkhateeb,
  • Asmaa Mostafa,
  • Ahmed Nassar,
  • Ahmed Mady,
  • Sohaila Elmihy,
  • Nadia M. Hamdy,
  • Sohaila M. Khalil

摘要

Leukemias are a group of hematologic malignancies that originate in the bone marrow (BM) in an acute or chronic manner, leading to an abnormal expansion of white blood cells due to abnormalities in lymphoid or myeloid progenitors. Leukemic stem cells (LSCs), a rare subpopulation, originate from cancer stem cells (CSCs) and represent a major contributor to the relapse of leukemia. These cells possess the characteristics of stem cells, including self-renewal, quiescence, and resistance to chemotherapy. They frequently reside in the CD34+CD38− compartment. Certain surface markers, such as CD123, CD44, CD47, TIM-3, CLL-1, and CD96, can identify LSCs and differentiate them from healthy hematopoietic stem cells (HSCs). These markers could also serve as therapeutic targets. The abnormal activation of important developmental and oncogenic pathways, including Wingless-related integration site (WNT)/β-catenin, Hedgehog, Notch, PI3K/Protein Kinase B (AKT)/mTOR, and NF-κB, controls the survival and maintenance of LSCs. This is frequently done in conjunction with epigenetic changes and metabolic rewiring. These pathways, in addition to other pathways such as Transforming growth factor (TGF)-β, TLR and p53, are implicated in the biology of LSCs and contribute to the escape of LSCs from immune cells as well as their persistence during remission. Recent studies have advanced our understanding of LSC biology and the development of several drugs that can target LSCs based on specific phenotypic and molecular characteristics. Despite these developments, challenges including immune evasion, phenotypic plasticity, and bone marrow protection still exist. This chapter will focus on a deeper understanding of the unique cellular and molecular LSC signatures and their roles in poor prognosis and disease relapse, as well as on the potential drugs that target either LSC markers or certain pathways in LSCs.