Molecular signatures of chronic myeloid leukemia stem cells

Yaoyu Chen,Shaoguang Li

doi:10.1186/2050-7771-1-21

Abstract

BCR-ABL tyrosine kinase inhibitors (TKIs) are effective in controlling Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) are unlikely to cure the disease because TKIs are unable to eradicate leukemia stem cells (LSCs) responsible for the disease relapse even after tyrosine kinase inhibition. In addition, the TKI resistance of LSCs is not associated with the BCR-ABL kinase domain mutations. These observations indicate that TKI-insensitive LSCs and TKI-sensitive leukemic progenitor cells are biologically different, which leads us to believe that LSCs and more differentiated leukemic cells have different genetic mechanisms. Further study of LSCs to identify the novel gene signatures and mechanisms that control the function and molecular phenotype of LSCs is critical. In this mini-review, we will discuss our current understanding of the biology of LSCs and novel genes that could serve as a molecular signature of LSCs in CML. These novel genes could also serve as potential targets for eradicating LSCs in CML.

Highlights

Human Philadelphia chromosome-positive (Ph+) leukemia induced by the BCR-ABL oncogene is the most common myeloproliferative disorder known as chronic myeloid leukemia (CML)
CML starts with a chronic phase and progresses to a more acute terminal phase called “blast crisis” resulting in development of acute myeloid or acute B-lymphoid leukemia, which is characterized by granulocytosis and splenomegaly
The rate of complete cytogenetic response among patients receiving imatinib was 87% after 5 years of treatment [3]. It effectively inhibits the BCR-ABL kinase activity and improves the survival of CML patients, imatinib does not appear to lead to a cure of the disease, because patients in complete cytogenetic remission after imatinib treatment still contain BCR-ABL-expressing leukemia cells

Summary

Introduction

Human Philadelphia chromosome-positive (Ph+) leukemia induced by the BCR-ABL oncogene is the most common myeloproliferative disorder known as chronic myeloid leukemia (CML). By using the CML mouse model, BCR-ABL-expressing Lin-c-Kit+Sca-1+ cells were shown to function as LSCs in chronic phase CML [15]. Human CML stem cells do not depend on BCR-ABL kinase activity for survival and are not eliminated by imatinib therapy.

Results

Conclusion