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➡️Light-chain amyloidosis (AL) and multiple myeloma (MM), are plasma cell (PC) malignancies with strikingly different clinical presentations 🥼🩺
➡️Success in🎯identifying these mechanisms has thus far been limited 👎
➡️Light-chain amyloidosis (AL) and multiple myeloma (MM), are plasma cell (PC) malignancies with strikingly different clinical presentations 🥼🩺
➡️Success in🎯identifying these mechanisms has thus far been limited 👎
(2/14)
➡️Alameda et al define a “transcriptional atlas” of normal PCs, AL amyloidosis, MM, and MGUS, identifying 13 different transcriptional patterns linking distinct PC dyscrasias to subsets of normal developing PCs, with diagnostic 🔬and prognostic implications
➡️Alameda et al define a “transcriptional atlas” of normal PCs, AL amyloidosis, MM, and MGUS, identifying 13 different transcriptional patterns linking distinct PC dyscrasias to subsets of normal developing PCs, with diagnostic 🔬and prognostic implications
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➡️This is the☝️first integrated bulk and single-cell analysis of the transcriptional programs of anatomically different normal PC subsets vs tumour PCs in AL, MM, and MGUS.👇
➡️This is the☝️first integrated bulk and single-cell analysis of the transcriptional programs of anatomically different normal PC subsets vs tumour PCs in AL, MM, and MGUS.👇
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👉💯 subjects were studied
Normal PCs were isolated by fluorescence-activated cell sorting (FACS) from SLOs and PB according to immunoglobulin heavy-chain isotypes, as well as from BM samples of healthy adults according to differential expression of CD19, CD39, CD56,&CD81
👉💯 subjects were studied
Normal PCs were isolated by fluorescence-activated cell sorting (FACS) from SLOs and PB according to immunoglobulin heavy-chain isotypes, as well as from BM samples of healthy adults according to differential expression of CD19, CD39, CD56,&CD81
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👉Tumor PCs were isolated by FACS from BM samples of patients with AL (n = 32), MGUS (n = 6), and MM (n = 32).
👉Ectoenzyme CD39 as a discriminatory biomarker of newborn BM-PCs.
👉Tumor PCs were isolated by FACS from BM samples of patients with AL (n = 32), MGUS (n = 6), and MM (n = 32).
👉Ectoenzyme CD39 as a discriminatory biomarker of newborn BM-PCs.
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➡️Tumour PCs express TPs linked to various stages of normal PC differentiation
➡️Nonsuperimposable distribution of tumour PCs from AL, MM, and MGUS patients 😷throughout the various stages of normal PC development
➡️Tumour PCs express TPs linked to various stages of normal PC differentiation
➡️Nonsuperimposable distribution of tumour PCs from AL, MM, and MGUS patients 😷throughout the various stages of normal PC development
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➡️TPs from SLOs, PB, and newborn and long-lived BM-PCs were equally distributed in MGUS, there was a predominant expression of TPs from SLO-PCs in AL and TPs from PB- plus newborn BM-PCs in MM
➡️TPs from SLOs, PB, and newborn and long-lived BM-PCs were equally distributed in MGUS, there was a predominant expression of TPs from SLO-PCs in AL and TPs from PB- plus newborn BM-PCs in MM
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➡️AL patients with tumour PCs displaying ⚡️higher NES values corresponding to normal SLO-PCs had significantly 🔽inferior progression-free survival
➡️AL patients with tumour PCs displaying ⚡️higher NES values corresponding to normal SLO-PCs had significantly 🔽inferior progression-free survival
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➡️What is known?🔖
👉📌AL and MM share a common causal root, namely, the presence of clonal malignant plasma cells in the bone marrow, but the behaviour of these cells differ
➡️What is known?🔖
👉📌AL and MM share a common causal root, namely, the presence of clonal malignant plasma cells in the bone marrow, but the behaviour of these cells differ
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👉📌In AL, the clonal plasma cells do not accumulate but induce the deposition of light chains in various organs
👉📌In MM, clonal plasma cells accumulate in the bone marrow, leading to harmful effects.
👉📌In AL, the clonal plasma cells do not accumulate but induce the deposition of light chains in various organs
👉📌In MM, clonal plasma cells accumulate in the bone marrow, leading to harmful effects.
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➡️What is unknown?🧐🔍
👉Mechanisms identifying differences in these plasma cell disorders is limited.
➡️What is unknown?🧐🔍
👉Mechanisms identifying differences in these plasma cell disorders is limited.
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➡️New Knowledge Generated 🔓🗝️
👉A predominant TP from SLO-PCs was expressed in AL, and from both PB-PCs and newborn BM-PCs in MM
👉TPs related to germinal centre formation & B-cell activation/proliferation were turned off once normal PCs exited from SLOs(TP-3 & TP-4)
➡️New Knowledge Generated 🔓🗝️
👉A predominant TP from SLO-PCs was expressed in AL, and from both PB-PCs and newborn BM-PCs in MM
👉TPs related to germinal centre formation & B-cell activation/proliferation were turned off once normal PCs exited from SLOs(TP-3 & TP-4)
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👉Genes related to NF-kB, were turned on from the moment PCs left SLOs
👉Impaired ribosome machinery in AL
👉Genes related to NF-kB, were turned on from the moment PCs left SLOs
👉Impaired ribosome machinery in AL
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➡️Take-Home📤🥡🏡
Tumour cells in light-chain amyloidosis and myeloma show different transcriptional rewiring of normal plasma cell development.
➡️Take-Home📤🥡🏡
Tumour cells in light-chain amyloidosis and myeloma show different transcriptional rewiring of normal plasma cell development.
🛑⏱️END OF #TWEETORIAL!!
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References:
1. Corre, J. (2021). Why is amyloidosis not multiple myeloma?. Blood, 138(17), 1514-1515. doi.org/10.1182/blood.…
1. Corre, J. (2021). Why is amyloidosis not multiple myeloma?. Blood, 138(17), 1514-1515. doi.org/10.1182/blood.…
2. Alameda, D., Goicoechea, I., Vicari, M., Arriazu, E., Nevone, A., & Rodriguez, S. et al. (2021). Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development. Blood, 138(17), 1583-1589. doi.org/10.1182/blood.…
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