Time to Move to the Single-Cell Level: Applications of Single-Cell Multi-Omics to Hematological Malignancies and Waldenström’s Macroglobulinemia—A Particularly Heterogeneous Lymphoma

Jiménez, Cristina

doi:10.3390/cancers13071541

Cited by 8 publications

(7 citation statements)

References 117 publications

(77 reference statements)

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“…Targeted therapies are especially prone to resistance with relatively simple mutations in the target protein or pathway, but thanks to methodological advances, we are starting to understand much more complex signaling networks that can create forms of resistance beyond classic genetics. Single-cell technologies, immune-phenotyping, single-cell transcriptome profiling, functional studies, and chromatin mapping, all integrated with bioinformatic analytic tools, may help understand the supportive role of the immune microenvironment in CLL progression and the co-evolution of cells involved in the disease, directly or indirectly [5,41,52,[82][83][84].…”

Section: Role Of the Immune System In Resistance To Treatmentmentioning

confidence: 99%

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Moreno¹,

Muñoz

Terol

et al. 2021

J Exp Clin Cancer Res

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Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient’s own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.

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Section: Role Of the Immune System In Resistance To Treatmentmentioning

confidence: 99%

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Moreno¹,

Muñoz

Terol

et al. 2021

J Exp Clin Cancer Res

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“…However, if we can assume that cellular heterogeneity plays a critical role in tissue behavior, omic data at single-cell resolution are needed and are within the reach of current technologies. Single-cell multiomic analyses have been most actively conducted in the clinical field of cancer and hematological diseases and have been successfully used in clarifying many unknown features of their etiologies [ 15 , 22 – 26 ].…”

Section: Multi-scale Structure Of the Biological System: Omic Measurement At Single Granularity May Uncover Hidden Aspects Of Transition mentioning

confidence: 99%

Multiomic technologies for analyses of inborn errors of immunity: from snapshot of the average cell to dynamic temporal picture at single-cell resolution

2021

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Advances in DNA sequencing technology have significantly impacted human genetics; they have enabled the analysis of genetic causes of rare diseases, which are usually pathogenic variants in a single gene at the nucleotide sequence level. However, since the quantity of data regarding the relationship between genotype and phenotype is insufficient to diagnose some rare immune diseases definitively, genetic information alone cannot help obtain a mechanistic understanding of the disease etiology. For such cases, exploring the molecular phenotype using multiomic analyses could be the approach of choice. In this review, we first overview current technologies for multiomic analysis, particularly focusing on RNA and protein profiling of bulk cell ensembles. We then discuss the measurement modality and granularity issue because it is critical to design multiomic experiments properly. Next, we illustrate the importance of bioimaging by describing our experience with the analysis of an autoinflammatory disease, cryopyrin-associated periodic fever syndrome, which could be caused by low-frequency somatic mosaicism and cannot be well characterized only by multiomic snapshot analyses of an ensemble of many immune cells. We found it powerful to complement the multiomic data with bioimaging data that can provide us with indispensable time-specific dynamic information of every single cell in the “immune cell society.” Because we now have many measurement tools in different modalities and granularity to tackle the etiology of rare hereditary immune diseases, we might gain a deeper understanding of the pathogenic mechanisms of these diseases by taking full advantage of these tools in an integrated manner.

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“…However, since the first whole-genome sequencing (WGS) of leukaemia in 2008 [8], the mutational landscape of haematological malignancies has proven to be both much more complex and heterogeneous with a shortage of targets as uniformly present and druggable as in CML. Also, intratumour heterogeneity and clonal evolution are increasingly recognised and likely to play a role in tumour progression as well as therapy resistance [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Application of precision medicine in clinical routine in haematology—Challenges and opportunities

et al. 2022

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Precision medicine is revolutionising patient care in cancer. As more knowledge is gained about the impact of specific genetic lesions on diagnosis, prognosis and treatment response, diagnostic precision and the possibility for optimal individual treatment choice have improved. Identification of hallmark genetic aberrations such as the BCR::ABL1 gene fusion in chronic myeloid leukaemia (CML) led to the rapid development of efficient targeted therapy and molecular follow‐up, vastly improving survival for patients with CML during recent decades. The assessment of translocations, copy number changes and point mutations are crucial for the diagnosis and risk stratification of acute myeloid leukaemia and myelodysplastic syndromes. Still, the often heterogeneous and complex genetic landscape of haematological malignancies presents several challenges for the implementation of precision medicine to guide diagnosis, prognosis and treatment choice. This review provides an introduction and overview of the important molecular characteristics and methods currently applied in clinical practice to guide clinical decision making in haematological malignancies of myeloid and lymphoid origin. Further, experimental ways to guide the choice of targeted therapy for refractory patients are reviewed, such as functional precision medicine using drug profiling. An example of the use of pipeline studies where the treatment is chosen according to the molecular characteristics in rare solid malignancies is also provided. Finally, the future opportunities and remaining challenges of precision medicine in the real world are discussed.

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Time to Move to the Single-Cell Level: Applications of Single-Cell Multi-Omics to Hematological Malignancies and Waldenström’s Macroglobulinemia—A Particularly Heterogeneous Lymphoma

Cited by 8 publications

References 117 publications

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Multiomic technologies for analyses of inborn errors of immunity: from snapshot of the average cell to dynamic temporal picture at single-cell resolution

Application of precision medicine in clinical routine in haematology—Challenges and opportunities

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