New approaches to molecular monitoring in CML (and other diseases)

Radich, Jerald P.; Yeung, Cecilia; Wu, David

doi:10.1182/blood.2019000838

Cited by 34 publications

(25 citation statements)

References 60 publications

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“…The main teaching of the countless clinical and biological studies conducted over all these years is that the cure of CML can only pass through the abrogation of the Ph+ clone, which can be detected and monitored by cytogenetics (chromosome banding analysis (CBA), or fluorescent in-situ hybridization (FISH)) or by real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) [ 6 , 7 , 8 ].…”

mentioning

confidence: 99%

Chronic Myeloid Leukemia Prognosis and Therapy: Criticisms and Perspectives

Russo

Garcia-Gutierrez

Soverini

et al. 2020

JCM

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Ph+ chronic myeloid leukemia (CML) is a clonal myeloproliferative disease whose clinical course is characterized by progression disease from the early chronic phase (CP) to the fatal blastic phase (BP). This programmed course is closely related to the translocation t(9;22)(q22;q11) and the resulting BCR-ABL1 fusion protein (p210) that drives the leukemic transformation of hematopoietic stem cells. Therefore, the cure of CML can only pass through the abrogation of the Ph+ clone. Allogeneic stem cell transplantation (allo-SCT) and interferon-alpha (IFNα) have been proven to reduce the Ph+ clone in a limited proportion of CML population and this translated in a lower rate of progression to BP and in a significant prolongation of survival. Tyrosine-kinase inhibitors (TKIs), lastly introduced in 2000, by preventing the disease blastic transformation and significantly prolonging the survival in up to 90% of the patient population, radically changed the fate of CML. The current therapy with TKIs induces a chronicization of the disease but several criticisms still persist, and the most relevant one is the sustainability of long-term therapy with TKIs in terms of compliance, toxicity and costs. The perspectives concern the optimization of therapy according to the age, the risk of disease, the potency and the safety profiles of the TKIs. The prolongation of survival is the most important end point which should be guaranteed to all patients. The treatment free remission (TFR) is the new goal that we would like to give to an increasing number of patients. The cure remains the main objective of CML therapy.

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mentioning

confidence: 99%

Chronic Myeloid Leukemia Prognosis and Therapy: Criticisms and Perspectives

Russo

Garcia-Gutierrez

Soverini

et al. 2020

JCM

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“…Breakthroughs in 'realtime' sequencing, such as Pacific Bioscience and Nanopore technology, which can read exceeding long sequences at breathtaking speeds, potentially allow BCR-ABL1 breakpoint detection to be performed with a single sequencing run. 8 In CML, there are two variants of the BCR-ABL1 transcript, depending on whether the break in BCR occurs in T.I. Mughal et al At diagnosis, methods can be used to quickly identify breakpoints useful for designing monitoring assays, as well as other mutations that might influence the initial response to treatment with a tyrosine kinase inhibitor.…”

Section: Clinically Validated Tests For Detecting and Monitoring Bcr-mentioning

confidence: 99%

“… 6 Some of these achievements have been facilitated by the rational integration of next-generation sequencing (NGS) assays, high-sensitive polymerase chain reaction (PCR) assays on DNA or RNA (sensitivity 0.01%- 0.1%), and single-cell analyses, in efforts to improve personalized treatment approaches. 8 Such efforts have opened a new era of precision medicine for diverse malignancies in which relatively non-specific and often toxic drugs are being replaced by safer and better tolerated agents whose mechanism of action is precisely defined, and for which the treatment algorithm is guided by individual genetic information. Here we examine how molecular testing in MPN can shape diagnosis, monitoring, and treatment algorithms and enable more precise early identification of targeted therapy resistance, particularly in CML ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Interrogating the molecular genetics of chronic myeloproliferative malignancies for personalized management in 2021

et al. 2021

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“…Leukemia can be categorized into different subtypes depending on the progression of the disease (acute and chronic) or a lineage and developmental stage of cells (myeloid or lymphoblastic). Four main subtypes of leukemia that will be discussed in this review are: acute lymphoblastic leukemia (ALL) (12-14), AML (15,16), chronic lymphocytic leukemia (CLL) (17,18), and chronic myeloid leukemia (CML) (19,20). Leukemic cells have been described to interact with and remodel BM to support leukemic cell expansion and survival (21).…”

Section: Leukemia and Leukemia Stem Cellsmentioning

confidence: 99%

Cadherins, Selectins, and Integrins in CAM-DR in Leukemia

et al. 2020

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The interaction between leukemia cells and the bone microenvironment is known to provide drug resistance in leukemia cells. This phenomenon, called cell adhesion-mediated drug resistance (CAM-DR), has been demonstrated in many subsets of leukemia including B- and T-acute lymphoblastic leukemia (B- and T-ALL) and acute myeloid leukemia (AML). Cell adhesion molecules (CAMs) are surface molecules that allow cell–cell or cell–extracellular matrix (ECM) adhesion. CAMs not only recognize ligands for binding but also initiate the intracellular signaling pathways that are associated with cell proliferation, survival, and drug resistance upon binding to their ligands. Cadherins, selectins, and integrins are well-known cell adhesion molecules that allow binding to neighboring cells, ECM proteins, and soluble factors. The expression of cadherin, selectin, and integrin correlates with the increased drug resistance of leukemia cells. This paper will review the role of cadherins, selectins, and integrins in CAM-DR and the results of clinical trials targeting these molecules.

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New approaches to molecular monitoring in CML (and other diseases)

Abstract: In a review article, the authors discuss the present and future of molecular testing in chronic myeloid leukemia (CML) as a paradigm of the evolution of technologies assisting in better diagnosis, risk stratification, and response monitoring of leukemia and other cancers.

Cited by 34 publications

References 60 publications

Chronic Myeloid Leukemia Prognosis and Therapy: Criticisms and Perspectives

Chronic Myeloid Leukemia Prognosis and Therapy: Criticisms and Perspectives

Interrogating the molecular genetics of chronic myeloproliferative malignancies for personalized management in 2021

Cadherins, Selectins, and Integrins in CAM-DR in Leukemia

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