[Progress in the studies of acute myelogenous leukemia stem cell].
Acute myelogenous leukemia (AML) cells are organized in a hierarchical fashion, with only the most primitive rare population (leukemia stem cell, LSC) of AML cells capable of maintaining the leukemic clone. A broad range of studies has indicated that AML results from mutations at the level of the stem cells of AML cells. The changes of cellular and molecular features in these malignant stem cells determine the features of leukemic clone and give rise to different subtypes of AML. LSCs share some similar characteristics with normal hematopoietic stem cells (HSC) including the ability to self-renew, and also have the potential of limited differentiation. LSCs, also have some features that are not found in normal HSC. LSCs have unique phenotype such as CD90-, CD117- and CD123+. Tumor-suppressor protein-death associated protein kinase and interferon regulatory factor 1 were overexpressed in LSCs, but not in normal HSC. Due to a predominantly G0 cell-cycle status, LSCs may not be responsive to conventional chemotherapeutic agents, compared with leukemia blasts. It is proposed that surviving LSCs are a major contributing factor to leukemic relapse. Although LSC population is likely to be drug-resistant, quiescent LSCs are preferentially susceptible to apoptosis induction while sparing normal HSC, with the appropriate stimulus such as proteasome inhibitor MG-132. This article reviewed the data emerging from the study of LSCs, and elucidated the distinct cellular and molecular characteristics of the LSC population, which may shed new light on AML therapy and leukemogenesis study.
Department of Hematology, the First Clinical Hospital of Jilin University, Changchun 130021, China.
Jiu-Wei
JW
Cui
Xue-Min
XM
Zhang
Guan-Jun
GJ
Wang
D002452:Cell Count; D002453:Cell Cycle; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis