Abstract
The use of tyrosine kinase inhibitors (TKI) such as imatinib mesylate (IM) targeted against BCR-ABL has proven successful in chronic myeloid leukemia (CML) and long-term survival has become a reality. However, several mathematical models and ex-vivo examinations suggested that IM-therapy does not eradicate CML stem cells. We recently reported the investigation of residual CML diseases during TKI treatment using FACS-sorting and quantitative RT-PCR of BCR-ABL among each population; total mononuclear cells, hematopoietic stem cells, and myeloid progenitors. Moreover, we need to develop the evaluation method of the residual CML stem cells to establish rational TKI-cessation strategies in CML.
Highlights
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of a fusion oncogene, BCR-ABL, which encodes a protein with constitutive tyrosine kinase activity [1]
Cells within hematopoietic hierarchy can be distinguished by their proliferative and differentiation activity which they display under conditions designed to optimally elicit these, either in vivo or in vitro [5,6]
The autocrine secretion of IL-3 and Granulocyte colony stimulating factor (G-CSF) by primitive leukemic progenitors likely contributes to growth advantage of leukemic myeloid progenitors and mature cells in patients resulting in their dominance of peripheral blood and bone marrow of newly diagnosed CML patients with mature CML cells [6]
Summary
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of a fusion oncogene, BCR-ABL, which encodes a protein with constitutive tyrosine kinase activity [1]. The mechanisms for TKI insensitivity of CML stem remains unclear; factors such as quiescence, high level of BCR-ABL expression, acquired mutations in the oncogene, and overexpression of membrane transporter proteins in these cells may play a role [2,3,4]. Myelopoiesis is sustained through the life by the regulated proliferative and differentiation activity of a large pool of hematopoietic stem cells (HSCs) (Figure 1A).
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