Measurable residual disease in chronic myeloid leukemia

Branford, Susan; Apperley, Jane F.

doi:10.3324/haematol.2022.281493

Cited by 9 publications

(8 citation statements)

References 96 publications

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“…Digital droplet PCR (ddPCR), which has emerged recently, uses a water–oil emulsion droplet system that divides the sample into thousands of individually repeated PCRs. 16 This high repeatability significantly improves the sensitivity of detection and is not affected by amplification differences.…”

Section: Monitoring Before Tki Discontinuationmentioning

confidence: 96%

“…Currently, qRT‐PCR is used internationally as the gold standard for detecting BCR::ABL transcripts, 15 and its detection results are used as important indicators for evaluating the efficacy and prognosis of patients with CML. Digital droplet PCR (ddPCR), which has emerged recently, uses a water–oil emulsion droplet system that divides the sample into thousands of individually repeated PCRs 16 . This high repeatability significantly improves the sensitivity of detection and is not affected by amplification differences.…”

Section: Monitoring Before Tki Discontinuationmentioning

confidence: 99%

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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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Section: Monitoring Before Tki Discontinuationmentioning

confidence: 96%

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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“…At 10 years, the OS is stil 82%-85%, but the resistance rate to IM in first-line patients is 10%-15%, and the resistance rate to second-generation TKI is < 10% 5 . Summarizing multiple studies worldwide, mutations in the ABL kinase domain accounts for about 22.4%-54.46% of resistance CML patients, with p-loop mutations accounting for about one-fourth 6 , 7 .…”

Section: Epidemiologymentioning

confidence: 99%

“…Influx transporters include organic cation transporter 1 (OCT1 or SLC22A1), organic anion-transporting polypeptide 1A2 (SCL01A2 or OATP1A2), OCTN2 and MATE1 46 , 51 . OCT1 is the main transporter responsible for TKI uptake, and its expression or activity affects the level of drug response 7 , 13 , 27 . Other transporters have been identified as intermediaries in TKI transportation.…”

Section: Mechanisms Of Tki Resistancementioning

confidence: 99%

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia

Sun,

Hu,

Han

et al. 2024

Int. J. Biol. Sci.

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Chronic myeloid leukemia (CML) is a malignant clonal disease involving hematopoietic stem cells that is characterized by myeloid cell proliferation in bone marrow and peripheral blood, and the presence of the Philadelphia (Ph) chromosome with BCR-ABL fusion gene. Treatment of CML has dramatically improved since the advent of tyrosine kinase inhibitors (TKI). However, there are a small subset of CML patients who develop resistance to TKI. Mutations in the ABL kinase domain (KD) are currently recognized as the leading cause of TKI resistance in CML. In this review, we discuss the concept of resistance and summarize recent advances exploring the mechanisms underlying CML resistance. Overcoming TKI resistance appears to be the most successful approach to reduce the burden of leukemia and enhance cures for CML. Advances in new strategies to combat drug resistance may rapidly change the management of TKI-resistant CML and expand the prospects for available therapies.

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“…Despite its growing importance, MRD data are often excluded from U.S. prescribing information because of analytical, validation, and trial design complexities [ 97 ]. However, incorporation of MRD as an endpoint in phase II clinical trials for hematological malignancies is gaining momentum and consideration [ 98 ].…”

Section: Introductionmentioning

confidence: 99%

Bridging horizons beyond CIRCULATE-Japan: a new paradigm in molecular residual disease detection via whole genome sequencing-based circulating tumor DNA assay

Hashimoto,

Nakamura,

Oki

et al. 2024

Int J Clin Oncol

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Circulating tumor DNA (ctDNA) is the fraction of cell-free DNA in patient blood that originates from a tumor. Advances in DNA sequencing technologies and our understanding of the molecular biology of tumors have increased interest in exploiting ctDNA to facilitate detection of molecular residual disease (MRD). Analysis of ctDNA as a promising MRD biomarker of solid malignancies has a central role in precision medicine initiatives exemplified by our CIRCULATE-Japan project involving patients with resectable colorectal cancer. Notably, the project underscores the prognostic significance of the ctDNA status at 4 weeks post-surgery and its correlation to adjuvant therapy efficacy at interim analysis. This substantiates the hypothesis that MRD is a critical prognostic indicator of relapse in patients with colorectal cancer. Despite remarkable advancements, challenges endure, primarily attributable to the exceedingly low ctDNA concentration in peripheral blood, particularly in scenarios involving low tumor shedding and the intrinsic error rates of current sequencing technologies. These complications necessitate more sensitive and sophisticated assays to verify the clinical utility of MRD across all solid tumors. Whole genome sequencing (WGS)-based tumor-informed MRD assays have recently demonstrated the ability to detect ctDNA in the parts-per-million range. This review delineates the current landscape of MRD assays, highlighting WGS-based approaches as the forefront technique in ctDNA analysis. Additionally, it introduces our upcoming endeavor, WGS-based pan-cancer MRD detection via ctDNA, in our forthcoming project, SCRUM-Japan MONSTAR-SCREEN-3.

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Measurable residual disease in chronic myeloid leukemia

Cited by 9 publications

References 96 publications

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

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

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia

Bridging horizons beyond CIRCULATE-Japan: a new paradigm in molecular residual disease detection via whole genome sequencing-based circulating tumor DNA assay

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