Work

Retention of CD34+ CML stem/progenitor cells during imatinib treatment and rapid decline after treatment with second-generation BCR–ABL inhibitors

Year: 2012

Type: article

Abstract: ABL-tyrosine kinase inhibitor (TKI), imatinib (IM) is suggested to be effective for proliferating leukemic cells, not quiescent chronic myeloid leukemia (CML) stem cells. 1 , 2 , 3 Recent clinical trials suggest that CML treatment can be improved with more potent BCR–ABL inhibition during the second generation of ABL-tyrosine kinase inhibitors (2nd-TKIs) such as dasatinib and nilotinib. 4 To comparatively examine the effects of IM and 2nd-TKIs on the BCR–ABL-positive hematopoietic stem cells (HSC) and progenitors, we investigated 47 CML-chronic phase cases using methods previously reported with FACSAria and quantitative real-time-PCR of BCR–ABL among each sorted population: total mononuclear cells, HSC/Thy-1 + , HSC/Thy-1 − , common myeloid progenitors, granulocyte macrophage progenitors and megakaryocyte erythroid progenitors (detailed in Supplementary Materials and Methods ). 5 , 6 By using this method in the HSC population, more than 30% of cells are supposed to have stem cell potential, probably as long-term culture-initiating cells. 7

Source: Leukemia

DOI: 10.1038/leu.2012.73