CombiFlow: combinatorial AML-specific plasma membrane expression profiles allow longitudinal tracking of clones

Houtsma, Roos; Meer, Nisha K. van der; Meijer, Kees; Morsink, Linde M.; Hogeling, Shanna M.; Woolthuis, Carolien M.; Ammatuna, Emanuele; Nijk, Marije T.; Boer, Bauke de; Huls, Gerwin; Mulder, André B.; Schuringa, Jan Jacob

doi:10.1182/bloodadvances.2021005018

Cited by 4 publications

(3 citation statements)

References 39 publications

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“…The IL-1RAP protein has been shown to be overexpressed on the surface of leukemic stem cells (LSCs) of AML, myelodysplastic syndrome and chronic myeloid leukemia (CML) but not on normal HSCs 10 11 and to be an interesting minimal residual disease markers. 12 In a previous work, we have confirmed absence of IL-1RAP detection of normal HSC, and functionally, we have shown, in vitro, by colony-forming cell assay and in vivo using an immunosafety cord blood engrafted murine model, that autologous IL-1RAP cocultured with HSC or infused in mice with partial human hematopoiesis do not target normal HSC and thus do not affect hematopoiesis recovery, except lower recovery of monocytes. 13 It is a proinflammatory protein that has an oncogenic effect in AML via the FLT3 and C-kit pathways 14 that promotes leukemic proliferation over normal hematopoiesis 15 and has been shown to be related to some solid tumors.…”

Section: Introductionsupporting

confidence: 66%

Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia

Trad

Warda

Alcazer

et al. 2022

J Immunother Cancer

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BackgroundAcute myeloid leukemia (AML) remains a very difficult disease to cure due to the persistence of leukemic stem cells (LSCs), which are resistant to different lines of chemotherapy and are the basis of refractory/relapsed (R/R) disease in 80% of patients with AML not receiving allogeneic transplantation.MethodsIn this study, we showed that the interleukin-1 receptor accessory protein (IL-1RAP) protein is overexpressed on the cell surface of LSCs in all subtypes of AML and confirmed it as an interesting and promising target in AML compared with the most common potential AML targets, since it is not expressed by the normal hematopoietic stem cell. After establishing the proof of concept for the efficacy of chimeric antigen receptor (CAR) T-cells targeting IL-1RAP in chronic myeloid leukemia, we hypothesized that third-generation IL-1RAP CAR T-cells could eliminate AML LSCs, where the medical need is not covered.ResultsWe first demonstrated that IL-1RAP CAR T-cells can be produced from AML T-cells at the time of diagnosis and at relapse. In vitro and in vivo, we showed the effectiveness of IL-1RAP CAR T-cells against AML cell lines expressing different levels of IL-1RAP and the cytotoxicity of autologous IL-1RAP CAR T-cells against primary cells from patients with AML at diagnosis or at relapse. In patient-derived relapsed AML xenograft models, we confirmed that IL-1RAP CAR T-cells are able to circulate in peripheral blood and to migrate in the bone marrow and spleen, are cytotoxic against primary AML cells and increased overall survival.ConclusionIn conclusion, our preclinical results suggest that IL-1RAP CAR T-based adoptive therapy could be a promising strategy in AML treatment and it warrants the clinical investigation of this CAR T-cell therapy.

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Section: Introductionsupporting

confidence: 66%

Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia

Trad

Warda

Alcazer

et al. 2022

J Immunother Cancer

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“…Thus, in AML, CD97 on leukemic stem cells is a promising therapeutic target. Furthermore, CD97 is a marker used in panels to monitor minimal residual disease in AML [87,88]…”

Section: Cd97 In Leukemiasmentioning

confidence: 99%

To Detach, Migrate, Adhere, and Metastasize: CD97/ADGRE5 in Cancer

Aust

Zheng

Quaas

2022

Cells

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Tumorigenesis is a multistep process, during which cells acquire a series of mutations that lead to unrestrained cell growth and proliferation, inhibition of cell differentiation, and evasion of cell death. Growing tumors stimulate angiogenesis, providing them with nutrients and oxygen. Ultimately, tumor cells invade the surrounding tissue and metastasize; a process responsible for about 90% of cancer-related deaths. Adhesion G protein-coupled receptors (aGPCRs) modulate the cellular processes closely related to tumor cell biology, such as adhesion and detachment, migration, polarity, and guidance. Soon after first being described, individual human aGPCRs were found to be involved in tumorigenesis. Twenty-five years ago, CD97/ADGRE5 was discovered to be induced in one of the most severe tumors, dedifferentiated anaplastic thyroid carcinoma. After decades of research, the time has come to review our knowledge of the presence and function of CD97 in cancer. In summary, CD97 is obviously induced or altered in many tumor entities; this has been shown consistently in nearly one hundred published studies. However, its high expression at circulating and tumor-infiltrating immune cells renders the systemic targeting of CD97 in tumors difficult.

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“…Despite skepticism regarding the quality of imputed MFC data, we identified 15 studies in which Infinicyt's "Calculate Data" module was used [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] (Table S1) to impute missing MFC markers. Out of these, only one publication contained a validation experiment that measured the imputed markers together.…”

Section: Introductionmentioning

confidence: 99%

Merging and imputation of flow cytometry data: A critical assessment

Mocking,

Duetz,

van Kuijk

et al. 2023

Cytometry Pt A

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Although most modern techniques and analysis methods in multiparameter flow cytometry (MFC) allow for increased dimensionality for the characterization and quantification of cell populations, most MFC applications depend on flow cytometers measuring relatively small (<16) numbers of parameters. When more markers than the available parameters need to be acquired, these are commonly distributed over multiple independent measurements that include a backbone of common markers. Several methods have been proposed to impute values for combinations of markers that were not measured simultaneously. These imputation methods are frequently used without proper validation and knowledge of their effects on data analysis. We evaluated the performance of existing imputation software (Infinicyt, CyTOFmerge, CytoBackBone, and cyCombine) in approximating known measured expression data in terms of similarity in visual appearance, cell expression, and gating in different datasets by splitting MFC samples into separate measurements with partially overlapping markers and re‐calculating missing marker expression. Out of the assessed packages, CyTOFmerge showed the most accurate approximation of the known expression in terms of similar expression values and concordance with manual gating, with a mean F‐score between 0.53 and 0.87 when retrieving cell populations in different datasets. Performance remained inadequate for all methods, with only limited similarity at the cell level. In conclusion, the use of imputed MFC data should take such limitations into account and include independent validation of results to justify conclusions.

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CombiFlow: combinatorial AML-specific plasma membrane expression profiles allow longitudinal tracking of clones

Cited by 4 publications

References 39 publications

Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia

Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia

To Detach, Migrate, Adhere, and Metastasize: CD97/ADGRE5 in Cancer

Merging and imputation of flow cytometry data: A critical assessment

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