Monitoring of leukemia stem cells in chronic myeloid leukemia patients

Cui, Jieke; Zhu, Zunmin; Liu, Songya; Li, Qing; Li, Meng; Cheng, Hui; Zhong, Zhaodong; Li, Weiming; You, Yong; Zhu, Xiaojian; Zou, Ping

doi:10.1080/10428194.2017.1421755

Cited by 9 publications

(8 citation statements)

References 11 publications

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“…This suggests that CML stem cells are continuously cleared by TKI therapy at a low rate or exist in a quiescent, insensitive state and stochastically pass through a transient-sensitive state. Interestingly, it is likely that most individuals in a TFR continue to harbor low-level residual disease when measured using ultrasensitive methodology (Bocchia et al, 2018;Cui et al, 2018). Therefore, it may be that once the CML stem cell number is reduced below a certain threshold, many individuals will experience long-term remission, either owing to the quiescent nature of the CML stem cell itself or immune-mediated disease control.…”

Section: Cancer Cellmentioning

confidence: 99%

Response and Resistance to BCR-ABL1-Targeted Therapies

2020

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Chronic myeloid leukemia (CML), caused by constitutively active BCR-ABL1 fusion tyrosine kinase, has served as a paradigm for successful application of molecularly targeted cancer therapy. The development of the tyrosine kinase inhibitor (TKI) imatinib allows patients with CML to experience near-normal life expectancy. Specific point mutations that decrease drug binding affinity can produce TKI resistance, and secondand third-generation TKIs largely mitigate this problem. Some patients develop TKI resistance without known resistance mutations, with significant heterogeneity in the underlying mechanism, but this is relatively uncommon, with the majority of patients with chronic phase CML achieving long-term disease control. In contrast, responses to TKI treatment are short lived in advanced phases of the disease or in BCR-ABL1-positive acute lymphoblastic leukemia, with relapse driven by both BCR-ABL1 kinase-dependent and -independent mechanisms. Additionally, the frontline CML treatment with second-generation TKIs produces deeper molecular responses, driving disease burden below the detection limit for a greater number of patients. For patients with deep molecular responses, up to half have been able to discontinue therapy. Current efforts are focused on identifying therapeutic strategies to drive deeper molecular responses, enabling more patients to attempt TKI discontinuation.

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Section: Cancer Cellmentioning

confidence: 99%

Response and Resistance to BCR-ABL1-Targeted Therapies

2020

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“…Considerable data indicate most if not all persons in TFR have some or even many residual CML LSCs as currently-defined including detection of BCRABL1 transcripts with sensitive technique such as digital polymerase chain reaction [23, 24]. These data support two conclusions: (1) it may not be necessary to eradicate all CML LSCs to achieve TFR in at least some people with CML; and (2) some or perhaps all of what we currently define as CML LSCs are resistant to killing by TKIs and can persist in persons in deep molecular remission including those able to stop TKI-therapy without CML recurrence.…”

Section: Is Targeting CML Lscs Clinically Important?mentioning

confidence: 99%

“…Some studies report CML LSCs are present at diagnosis, during therapy and in persons who are in TFR. Other studies discussed the correlation between CML LSC detection and probability of achieving TFR, but this is controversial [23, 24].…”

Section: Introductionmentioning

confidence: 99%

Chronic myeloid leukemia stem cells

et al. 2019

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Chronic myeloid leukemia (CML) is caused by BCRABL1 in a cell with the biological potential, intrinsic or acquired, to cause leukemia. This cell is commonly termed the CML leukemia stem cell (LSC). In humans a CML LSC is operationally-defined by ≥1 in vitro or in vivo assays of human leukemia cells transferred to immune-deficient mice. Results of these assays are sometimes discordant. There is also the unproved assumption that biological features of a CML LSC are stable. These considerations make accurate and precise identification of a CML LSC difficult or impossible. In this review, we consider biological features of CML LSCs defined by these assays. We also consider whether CML LSCs are susceptible to targeting by tyrosine kinase inhibitors (TKIs) and other drugs, and whether elimination of CML LSCs is needed to achieve therapy-free remission or cure CML.

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“…Although the ideal situation for attempting TFR is to clear the LSC from the body, there is currently no treatment specific to LSCs in the clinic. However, several clinical trials have found residual CML LSCs in most patients who maintain TFR, even when BCR::ABL is monitored using a highly sensitive assay, such as ddPCR 53,54 . The data suggested that LSCs are present even in patients who achieve DMR, and that TFR does not appear to require complete eradication of LSCs in at least a subset of patients.…”

Section: Monitoring Before Tki Discontinuationmentioning

confidence: 99%

Exploration of treatment‐free remission in CML, based on molecular monitoring

Zhang,

Zhou,

Zhou

et al. 2023

Cancer Medicine

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BackgroundTypical chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9; 22)(q34; q11) translocation. This chromosomal translocation forms the BCR::ABL1 fusion gene. The tyrosine kinase encoded by the BCR::ABL1 is considered to be the main pathogenic diver. BCR::ABL1 is not only a therapeutic target, but also a monitoring target. Monitoring of BCR::ABL1 reveals the progression of the disease and guides the next treatment. Now for CML, the target of treatment has been focused on treatment‐free remission (TFR).MethodsWe conducted a literature review of current developments of treatment‐free remission and molecular monitoring methods.ResultsMore effective and sensitive CML monitoring methods such as digital droplet PCR (ddPCR) and next generation sequencing (NGS) have further studied the measurable residual disease (MRD) and clonal heterogeneity, which provides strong support for the exploration of TFR. We discussed some of the factors that may be related to TFR outcomes at the molecular level, along with some monitoring strategies.ConclusionCurrently, predictive indicators for treatment‐free remission outcomes and recurrence are lacking in clinical practice. In future, treatment‐free remission research should focus on combining the clinical indicators with molecular monitoring and biological markers to personalize patient conditions and guide clinicians to develop individualized treatment plans, so that more patients with CML can achieve safer and stabler treatment‐free remission.

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Monitoring of leukemia stem cells in chronic myeloid leukemia patients

Cited by 9 publications

References 11 publications

Response and Resistance to BCR-ABL1-Targeted Therapies

Response and Resistance to BCR-ABL1-Targeted Therapies

Chronic myeloid leukemia stem cells

Exploration of treatment‐free remission in CML, based on molecular monitoring

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