bioRxiv : the preprint server for biology · 2026
'An NF2- wildtype malignant meningioma cell line for basic and translational science'.
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Chien Perry, Kohrn Brendan F, Nguyen Megan, Martins Timothy J, Emerson Samuel, Kennedy Scott R, Monnat Raymond J
Аннотация
BACKGROUND: Meningiomas are the most common primary nervous system neoplasm in adults. There are few good cellular models, especially of high grade/malignant meningiomas, to use to identify new therapeutic agents and treatment regimens. The widely available, partially characterized, NF2- wildtype ( NF2 wt) Grade 3 malignant meningioma cell line IOMM-Lee can help meet this need.
METHODS: We generated new data to better characterize IOMM-Lee genomic and mtDNA variants, proliferation rate and colony-forming efficiency and sensitivity to ionizing radiation as a function of ATM kinase activity. A screen of 349 anti-cancer drugs identified multiple, mechanistically distinct clinical use drugs with nanomolar IC 50 values and high drug sensitivity prediction scores.
RESULTS: Exome sequencing confirmed that IOMM-Lee is NF2wt , and contains a pathogenic TERT -promoter (c.-124C>T) variant. Population doubling times (PDT) were short (19-21 hrs), and colony forming efficiency (CFE) high, of up to 87%. IOMM-Lee is comparatively radiosensitive with a D 10 of ∼3.9 Gy, and could be radiosensitized by AZD-1390-mediated ATM kinase inhibition. Thirty-four anti-cancer compounds spanning several mechanistic classes were identified that potently suppressed cell proliferation at sub-micromolar IC 50 values with high Breeze 2.0 Drug Sensitivity Scores.
IMPORTANCE OF THE STUDY: We provide new data to better characterize IOMM-Lee, the most widely used cell line model of human Grade 3 malignant meningioma. These data identify and characterize IOMM-Lee genomic alterations and mtDNA variants; quantify growth kinetics and ionizing radiation sensitivity; and identify multiple mechanistically distinct, clinical use drugs with nanomolar IC 50 values, high drug sensitivity prediction scores and potential as meningioma systemic therapies. Our data more clearly locate IOMM-Lee in the landscape of genomically-defined meningiomas, and will aid better use of this experimentally tractable cell line model to understand meningioma biology and identify more effective malignant meningioma therapies and treatment regimens.
KEY POINTS: IOMM-Lee lacks NF2 mutations, though is clearly related to but distinct from many other meningiomas and meningioma cell lines. IOMM-Lee grows rapidly, is comparatively radio-sensitive, and can be suppressed by several mechanistic classes of anti-cancer agents at clinically achievable, sub-micromolar IC 50 values with high Drug Sensitivity Scores. The experimental tractability, simplicity and versatility of IOMM-Lee can facilitate analyses of many aspects of meningioma biology and therapeutic development across a wide range of in vitro , high throughput and in vivo xenograft/organoid protocols.
METHODS: We generated new data to better characterize IOMM-Lee genomic and mtDNA variants, proliferation rate and colony-forming efficiency and sensitivity to ionizing radiation as a function of ATM kinase activity. A screen of 349 anti-cancer drugs identified multiple, mechanistically distinct clinical use drugs with nanomolar IC 50 values and high drug sensitivity prediction scores.
RESULTS: Exome sequencing confirmed that IOMM-Lee is NF2wt , and contains a pathogenic TERT -promoter (c.-124C>T) variant. Population doubling times (PDT) were short (19-21 hrs), and colony forming efficiency (CFE) high, of up to 87%. IOMM-Lee is comparatively radiosensitive with a D 10 of ∼3.9 Gy, and could be radiosensitized by AZD-1390-mediated ATM kinase inhibition. Thirty-four anti-cancer compounds spanning several mechanistic classes were identified that potently suppressed cell proliferation at sub-micromolar IC 50 values with high Breeze 2.0 Drug Sensitivity Scores.
IMPORTANCE OF THE STUDY: We provide new data to better characterize IOMM-Lee, the most widely used cell line model of human Grade 3 malignant meningioma. These data identify and characterize IOMM-Lee genomic alterations and mtDNA variants; quantify growth kinetics and ionizing radiation sensitivity; and identify multiple mechanistically distinct, clinical use drugs with nanomolar IC 50 values, high drug sensitivity prediction scores and potential as meningioma systemic therapies. Our data more clearly locate IOMM-Lee in the landscape of genomically-defined meningiomas, and will aid better use of this experimentally tractable cell line model to understand meningioma biology and identify more effective malignant meningioma therapies and treatment regimens.
KEY POINTS: IOMM-Lee lacks NF2 mutations, though is clearly related to but distinct from many other meningiomas and meningioma cell lines. IOMM-Lee grows rapidly, is comparatively radio-sensitive, and can be suppressed by several mechanistic classes of anti-cancer agents at clinically achievable, sub-micromolar IC 50 values with high Drug Sensitivity Scores. The experimental tractability, simplicity and versatility of IOMM-Lee can facilitate analyses of many aspects of meningioma biology and therapeutic development across a wide range of in vitro , high throughput and in vivo xenograft/organoid protocols.