Dear Colleagues,

Until 20 years ago, before the advent of the era of tyrosine kinase therapies (TKI), chronic myeloid leukemia (CML) was a deadly hematological malignancy with a median survival of 3–5 years, with its only curative approach being allogeneic stem cell transplantation. The use of TKI therapies targeting the TK activity of BCR-ABL has revolutionized the natural history of the disease as well as its prognosis and has demonstrated, for the first time in the history of oncology, the power of targeted therapies for the treatment of human cancer. However, it has rapidly become clear that the use of TKI therapies alone cannot eradicate leukemic stem cells (LSC) which persist during therapy and lead to relapses upon the discontination of TKI in the majority of patients, an outcome that has now been shown in several TKI discontinuation trials. In addition, resistance to TKI therapies occurs in a fraction of patients, probably due to the genetic instablity inherent to BCR-ABL-expressing cells and their heterogeneity at diagnosis, and this leads to blast crisis. Recent major thechological advances, including novel stem cell models, single cell transcriptome/RNAseq data, and novel LSC/niche interaction methodologies allow currently unprecedented insight into the phenomenon of LSC persistence and heterogenity and may lead to the identification of novel targets and future curative strategies in the current decade.

In this Special Issue of IJMS, we aim to present contributions that shed light on the different mechanisms of CML stem cell persistence via the use of novel stem cell models and single cell experimental data as well as the identification of novel LSC–niche interactions and the molecular mechanisms involved in LSC persistence and resistance in CML.

Prof. Dr. Ali G. Turhan
Guest Editor

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• BCR-ABL
• leukemic stem cells
• single cell RNAseq
• patient-derived iPSC models
• niche models in CML
• leukemia–niche interactions
• mechanisms of immunosurveillance in CML
• identification of immune-repressive components of the CML niche