Endothelial cells: major players in acute myeloid leukaemia

Fodil, Sofiane; Arnaud, M.; Vaganay, Camille; Puissant, Alexandre; Lengliné, Etienne; Mooney, Nuala; Itzykson, Raphaël; Zafrani, Lara

doi:10.1016/j.blre.2022.100932

Cited by 13 publications

(6 citation statements)

References 209 publications

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“…In fact, there is evidence of active crosstalk between circulating tumor cells and endothelial cells in different organs. 19 Velocity of blood in the vasculature has an inverse relationship with vessels' cross-sectional area (volumetric flow rate [Q] = flow velocity • cross-sectional area). We suspect a reduction in blood velocity below the OCTA minimal detection threshold as a plausible cause of flow signal loss in our patients.…”

Section: Discussionmentioning

confidence: 99%

Retinal Microvascular Changes in Patients With Acute Leukemia

Cicinelli

Mastaglio

Menean

et al. 2022

Retina

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Purpose: To evaluate the retinal circulation in patients with active acute leukemia, to correlate the perfusion metrics with systemic laboratory values, and to assess the vascular perfusion after leukemia remission.Methods: Longitudinal study of 22 eyes from 12 patients with acute leukemia; healthy eyes were recruited as control subjects. All patients underwent optical coherence tomography angiography at baseline. Optical coherence tomography angiography was repeated in case of morphologic leukemia remission.Results: Patients' age ranged from 37 to 74 years. All participants had a 20/20 vision. In all leukemic eyes, optical coherence tomography angiography detected vascular alterations in the macula and the peripapillary region. Vessel density values in the superficial capillary plexus were lower in patients with leukemia than control subjects (46.8 ± 3.6 vs. 49.2 ± 2%, P = 0.08), irrespective of the presence of leukemic retinopathy (7 eyes, 32%). Lower vessel density was associated with lower white blood cells (P = 0.09) and lower platelets (P = 0.001). Reappearance of small capillaries, increase in vessel density, reduction in vessel diameter, and increase in fractal dimension were seen after remission.Conclusion: Subclinical, reversible reduction in vessel density and complexity on optical coherence tomography angiography occurs in patients with active acute leukemia and is presumably associated with bone marrow function failure. Further studies are warranted to explore its functional and prognostic significance.

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Section: Discussionmentioning

confidence: 99%

Retinal Microvascular Changes in Patients With Acute Leukemia

Cicinelli

Mastaglio

Menean

et al. 2022

Retina

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“…Here in T-ALL cells, we observe that LSC cells, more or less numerous in respectively BMAT-rich and -poor BM, are able to bind E-selectin in experimental models, very similar to cells being also detected in patients. It is reported that pro-inflammatory cytokines (TNF-α and IL-1β) enhance E-selectine expression in inflammed BM endothelium 42,56 . Associated with the fuel energy role of adipose tissue, adipocytokines, that include TNF-α and IL-1β which are highly expressed in BMAT 44 , must now be taken into consideration for their role in the microenvironment evolution after chemo/radiotherapy and aging 11,13,14,57 .…”

Section: Discussionmentioning

confidence: 99%

High CD44 expression identifies rare chemoresistant leukemic cells endowed with enhanced E-Selectin binding in T-ALL

Calvo,

Naguibneva,

Kypraios

et al. 2023

Preprint

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T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy characterized by an increased proliferation and incomplete maturation of T-cell progenitors. Despite therapeutic improvements, relapses are often of bad prognosis. Therapeutic vulnerabilities and chemoresistance mechanisms arising from cell plasticity induced by the bone marrow (BM) microenvironment remain an important field of investigation. Employing single cell RNA sequencing (scRNAseq) of human T-ALL cells recovered from adipocyte-rich and -poor BM, a distinct leukemic stem cell (LSC) population defined by quiescence and elevated CD44 level (Ki67neg/lowCD44high) expression is identified in both territories.In vivochemotherapy demonstrated that the LSC population evades drug treatment. Patient sample analyses confirmed the presence of Ki67neg/lowCD44highLSC both at diagnosis and relapse that displayed a specific transcriptomic signature. Interestingly, the intense expression of CD44 in T-ALL Ki67neg/lowLSC was associated with E-selectin binding. Importantly, when 39 human T-ALL samples were analyzed, the E-selectin binding ability was found significantly higher in Relapse/Refractory compared to drug-sensitive patients. These findings characterize a T-ALL LSC population with chemoresistant properties and shade light on new strategies for prognostic stratification while opening avenues for novel therapeutic options.

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“…Recent studies have highlighted the critical role of the BM vascular microenvironment in the development of chemotherapy resistance. 15 , 24 The vascular niche provides a protective environment for leukemia cells, enabling them to evade chemotherapy-induced damage. In particular, ECs play a crucial role in regulating the interactions between leukemia cells and their protective microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…AML cells secrete vascular endothelial growth factor (VEGF), 14 and the density of the BM microvasculature is increased in AML patients. 15,16 These findings highlight the importance of investigating the role of the microvasculature in AML development and progression and suggest that targeting these factors may be a promising avenue for future therapies.…”

Section: Introductionmentioning

confidence: 95%

Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia

et al. 2023

Blood Science

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Leukemia stem cells in acute myeloid leukemia (AML) can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy. In the context of AML, endothelial cells (ECs) are crucial components of these niches that appear to promote malignant expansion despite treatment. To better understand these interactions, we developed a real-time cell cycle-tracking mouse model of AML (Fucci-MA9) with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse. We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells, leading to relapse and proliferation. Importantly, post-chemotherapy resting leukemia cells tended to localize closer to blood vessels. Mechanistically, after chemotherapy, resting leukemia cells interacted with ECs, promoting their adhesion and anti-apoptotic capacity. Further, expression analysis of ECs and leukemia cells during AML, after chemotherapy, and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs. These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.

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Endothelial cells: major players in acute myeloid leukaemia

Cited by 13 publications

References 209 publications

Retinal Microvascular Changes in Patients With Acute Leukemia

Retinal Microvascular Changes in Patients With Acute Leukemia

High CD44 expression identifies rare chemoresistant leukemic cells endowed with enhanced E-Selectin binding in T-ALL

Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia

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