Human IL-6 fosters long-term engraftment of patient derived disease-driving myeloma cells in immunodeficient mice
Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells, developed serum M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Single cell RNA sequencing showed non-malignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma engrafted mice given CAR T-cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results establish NSG+hIL6 mice as an effective patient derived xenograft model for study and preclinical drug development of multiple myeloma and related plasma cell disorders.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 24. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hasanali, Zainul S [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 08.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2024.01.21.576547 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368173305 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368173305 | ||
| 003 | DE-627 | ||
| 005 | 20240208232216.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240208s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2024.01.21.576547 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1284.xml |
| 035 | |a (DE-627)NLM368173305 | ||
| 035 | |a (NLM)38328086 | ||
| 035 | |a (PII)2024.01.21.576547 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hasanali, Zainul S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Human IL-6 fosters long-term engraftment of patient derived disease-driving myeloma cells in immunodeficient mice |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 08.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells, developed serum M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Single cell RNA sequencing showed non-malignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma engrafted mice given CAR T-cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results establish NSG+hIL6 mice as an effective patient derived xenograft model for study and preclinical drug development of multiple myeloma and related plasma cell disorders | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Garfall, Alfred L |e verfasserin |4 aut | |
| 700 | 1 | |a Burzenski, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Shultz, Leonard D |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Kadu, Siddhant |e verfasserin |4 aut | |
| 700 | 1 | |a Sheppard, Neil C |e verfasserin |4 aut | |
| 700 | 1 | |a Dopkin, Derek |e verfasserin |4 aut | |
| 700 | 1 | |a Vogl, Dan T |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Adam D |e verfasserin |4 aut | |
| 700 | 1 | |a Waxman, Adam J |e verfasserin |4 aut | |
| 700 | 1 | |a Susanibar-Adaniya, Sandra P |e verfasserin |4 aut | |
| 700 | 1 | |a Carroll, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Stadtmauer, Edward A |e verfasserin |4 aut | |
| 700 | 1 | |a Allman, David |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2024) vom: 24. Jan. |w (DE-627)NLM31090014X |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:24 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2024.01.21.576547 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 24 |c 01 | ||