scholarly journals Chronic myeloid leukemia stem cells in the era of targeted therapies: resistance, persistence and long-term dormancy

Oncotarget ◽  
2011 ◽  
Vol 2 (9) ◽  
pp. 713-727 ◽  
Author(s):  
Jean-Claude Chomel ◽  
Ali G. Turhan
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Targeted Therapies ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cells

scholarly journals Leukemia Stem Cells as a Potential Target to Achieve Therapy-Free Remission in Chronic Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5822
Author(s):  
Kyoko Ito ◽  
Keisuke Ito
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Drug Binding ◽  
Leukemia Stem Cells ◽  
Phase Point ◽  
Hematopoietic Stem ◽  
Wide Range ◽  
Tki Resistance

Leukemia stem cells (LSCs, also known as leukemia-initiating cells) not only drive leukemia initiation and progression, but also contribute to drug resistance and/or disease relapse. Therefore, eradication of every last LSC is critical for a patient’s long-term cure. Chronic myeloid leukemia (CML) is a myeloproliferative disorder that arises from multipotent hematopoietic stem and progenitor cells. Tyrosine kinase inhibitors (TKIs) have dramatically improved long-term outcomes and quality of life for patients with CML in the chronic phase. Point mutations of the kinase domain of BCR-ABL1 lead to TKI resistance through a reduction in drug binding, and as a result, several new generations of TKIs have been introduced to the clinic. Some patients develop TKI resistance without known mutations, however, and the presence of LSCs is believed to be at least partially associated with resistance development and CML relapse. We previously proposed targeting quiescent LSCs as a therapeutic approach to CML, and a number of potential strategies for targeting insensitive LSCs have been presented over the last decade. The identification of specific markers distinguishing CML-LSCs from healthy HSCs, and the potential contributions of the bone marrow microenvironment to CML pathogenesis, have also been explored. Nonetheless, 25% of CML patients are still expected to switch TKIs at least once, and various TKI discontinuation studies have shown a wide range in the incidence of molecular relapse (from 30% to 60%). In this review, we revisit the current knowledge regarding the role(s) of LSCs in CML leukemogenesis and response to pharmacological treatment and explore how durable treatment-free remission may be achieved and maintained after discontinuing TKI treatment.

scholarly journals Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies

Leukemia ◽  
2007 ◽  
Vol 21 (5) ◽  
pp. 926-935 ◽  
Author(s):  
X Jiang ◽  
Y Zhao ◽  
C Smith ◽  
M Gasparetto ◽  
A Turhan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Targeted Therapies ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cells

scholarly journals Shedding Light on Targeting Chronic Myeloid Leukemia Stem Cells

2021 ◽  
Vol 10 (24) ◽  
pp. 5805
Author(s):  
Mohammad Houshmand ◽  
Alireza Kazemi ◽  
Ali Anjam Najmedini ◽  
Muhammad Shahzad Ali ◽  
Valentina Gaidano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Leukemia Stem Cells ◽  
Hematopoietic Stem ◽  
Long Term Treatment ◽  
Treatment Free Remission

Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors (TKI). When TKI therapy is discontinued in CML patients in deep, sustained and apparently stable molecular remission, these cells in approximately half of the cases restart to grow, resuming the leukemic process. The elimination of these TKI resistant leukemic stem cells is therefore an essential step in increasing the percentage of those patients who can reach a successful long-term treatment free remission (TFR). The understanding of the biology of the LSCs and the identification of the differences, phenotypic and/or metabolic, that could eventually allow them to be distinguished from the normal hematopoietic stem cells (HSCs) are therefore important steps in designing strategies to target LSCs in a rather selective way, sparing the normal counterparts.

scholarly journals Abstract 3117: CD80 can be the marker of chronic myeloid leukemia stem cells and regulated by BCR-ABL signaling

2021 ◽  
Author(s):  
Huixin Li ◽  
Shunichiro Yasuda ◽  
Satoru Aoyama ◽  
Chenyang Zhang ◽  
Yohei Kawano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cells

scholarly journals Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity

2011 ◽  
Vol 121 (3) ◽  
pp. 1222-1222 ◽  
Author(s):  
Amie S. Corbin ◽  
Anupriya Agarwal ◽  
Marc Loriaux ◽  
Jorge Cortes ◽  
Michael W. Deininger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cells

scholarly journals Defining niche interactions to target chronic myeloid leukemia stem cells

Haematologica ◽  
2020 ◽  
Vol 105 (1) ◽  
pp. 2-4
Author(s):  
Rebecca Mitchell ◽  
Mhairi Copland
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cells

scholarly journals The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells

2012 ◽  
Vol 44 (8) ◽  
pp. 861-871 ◽  
Author(s):  
Haojian Zhang ◽  
Cong Peng ◽  
Yiguo Hu ◽  
Huawei Li ◽  
Zhi Sheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cells
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