Defining the <i>in vivo</i> characteristics of acute myeloid leukemia cells behavior by intravital imaging

Duarte, Delfim; Amarteifio, Saoirse; Ang, Heather; Kong, Isabella Y.; Ruivo, Nicola; Pruessner, Gunnar; Hawkins, Edwin D.; Celso, Cristina Lo

doi:10.1111/imcb.12216

Cited by 22 publications

(18 citation statements)

References 24 publications

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“…In murine models, antagonism of the CXCL9and CXCL10-receptor CXCR3 was described to stop lung metastasis of breast cancer (Walser et al 2006). In preclinical and clinical trials, several antagonists of CXCR4 like AMD3100 have already been implied in pts with relapsed or refractory AML as a chemosentisizer or for stem-cell-mobilization with varying results (Duarte et al 2019;Rashidi and Uy 2015). Furthermore, smoldering type adult T-cell leukemia/lymphoma has been reported to be effectively treated with the anti-CC chemokine receptor 4 monoclonal antibody mogamulizumab (Nishikawa et al 2019).…”

Section: Role Of Chemokines In Tumor Immunology and In Immunotherapymentioning

confidence: 99%

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Merle

Fischbacher

Liepert

et al. 2019

Immunological Investigations

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In cancer or hematologic disorders, chemokines act as growth-or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, −9, −10, CCL2, −5, and IL-12 in AML/ MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blastproportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, −9, −10 and lower release of CCL2 and −5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2release at relapse were found compared to first diagnosispointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, −9, −10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and −5 but lower levels of CXCL8, −9, −10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, −9, −10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.

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Section: Role Of Chemokines In Tumor Immunology and In Immunotherapymentioning

confidence: 99%

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Merle

Fischbacher

Liepert

et al. 2019

Immunological Investigations

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“…Investigation into leukemic stem cells and their role in transferring functional resistance factors similarly remains a potential focus for future AML EV research. In vivo trafficking of EVs could also provide additional perspectives on how the chemoresistance phenotype is being transferred (85). While phenotypic changes have been observed due to the trafficking of miRNAs and other molecules via EVs, these EVs may additionally influence cells through novel ligand-receptor mediated mechanisms with EV surface molecules.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Extracellular Vesicles and Chemotherapy Resistance in the AML Microenvironment

et al. 2020

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Extracellular vesicle (EV) trafficking provides for a constitutive mode of cell-cell communication within tissues and between organ systems. Different EV subtypes have been identified that transfer regulatory molecules between cells, influencing gene expression, and altering cellular phenotypes. Evidence from a range of studies suggests that EV trafficking enhances cell survival and resistance to chemotherapy in solid tumors. In acute myeloid leukemia (AML), EVs contribute to the dynamic crosstalk between AML cells, hematopoietic elements and stromal cells and promote adaptation of compartmental bone marrow (BM) function through transport of protein, RNA, and DNA. Careful analysis of leukemia cell EV content and phenotypic outcomes provide evidence that vesicles are implicated in transferring several known key mediators of chemoresistance, including miR-155, IL-8, and BMP-2. Here, we review the current understanding of how EVs exert their influence in the AML niche, and identify research opportunities to improve outcomes for relapsed or refractory AML patients.

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“…The acquired longitudinal imaging results provided a comprehensive understanding of the complex cellular interactions between cancer cells and their surrounding environment. Furthermore, the collective migration and proliferation of cancer cells was observed over several weeks with detailed insights into cancer cell infiltration and disease progression providing valuable new targets and strategies for therapeutic interventions .…”

Section: Multiphoton Microscopy Of Cellular Dynamics In Living Bone Tmentioning

confidence: 99%

Intravital Multiphoton Imaging of the Bone and Bone Marrow Environment

Kim

Bixel

2019

Cytometry Pt A

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Over the last two decades, numerous advances in our understanding of bone cell biology and bone mineral homeostasis have been achieved. As a dynamic connective and supportive tissue, bone is constantly sensing and responding to both external mechanical forces and internal systemic and local signals. A variety of intravital imaging approaches have been investigated to identify molecular and cellular processes and to decipher signaling pathways involved in the cellular communication between different types of bone cells that form bone multicellular units. Furthermore, bone multicellular units interact with cells of the immune and hematopoietic system to maintain bone homeostasis. Bone-forming osteoblasts and bone-degrading osteoclasts are situated on the endosteal surface of bone influencing the dynamic remodeling and the regeneration of bone tissue. Osteocytes are found at very unique locations in the bone, closely surrounded by bone matrix, forming a cellular network through their interconnected dendritic processes. Bone marrow cells fill the numerous large cavities inside the bones with various blood cell lineages arising from hematopoietic stem and progenitor cells. A highly complex and interconnected network of arterial vessels and sinusoidal capillaries span through the bone marrow spaces forming an interface between the blood circulation and the bone marrow which allows cell trafficking between both compartments. Live imaging of animals using multiphoton microscopy represents a powerful approach to address the cellular behaviors of bone and bone marrow cells over time and space in their natural tissue microenvironment. The in vivo environment is crucial, because the dynamic behavior of cells is critically influenced by many tissue factors including extracellular components, cytokine and growth factor gradients, and fluid forces, such as blood flow. The review article focuses upon recent advances in multiphoton imaging technologies as well as novel experimental approaches in the understanding of the dynamic molecular and cellular mechanisms underlying bone tissue homeostasis, remodeling, and regeneration under physiological and pathological conditions.

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Defining the in vivo characteristics of acute myeloid leukemia cells behavior by intravital imaging

Cited by 22 publications

References 24 publications

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Extracellular Vesicles and Chemotherapy Resistance in the AML Microenvironment

Intravital Multiphoton Imaging of the Bone and Bone Marrow Environment

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