**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Raymond Comenzo, MD, Tufts Medical Center, Boston, MA

**Main Body of the Abstract**
Background Twenty percent of AL patients have marrow interstitial amyloid. [Am J Clin Pathol 120 (2003)]. We asked how the non-plasma cell marrow cells (CD138- MC) respond to amyloid.
Materials & Methods We compared CD138- MC from marrows with (+MA) and without (-MA) interstitial amyloid by gene expression profiling (GEP) and single-cell RNA-sequencing (scRNA-seq) and performed qPCR, immunoprecipitation (IP) and immunoblot (IB) for selected genes or proteins.
Results On review of biopsies of 49 AL patients, 22 were +MA and 27 –MA; 13 +MA and 16 –MA patients were newly diagnosed. The rest were in follow up.
GEP (+MA=3, -MA=3) showed no difference among genes for proteolytic enzymes or apolipoproteins between the groups. +MA cases had significantly up-regulated erythroid genes, including transmembrane and coiled-coil domain family 2 (TMCC2) as seen in the Volcano plot.(Figure 1A)  PCR confirmed the high expression of TMCC2.
With the scRNA-seq (+MA=4, -MA=4) comparison, in +MA marrows CD14+ monocytes and erythroid-megakaryocyte progenitors were increased and granulocyte-monocyte progenitors decreased by 66%. By gene enrichment studies in +MA marrows pathways for TNFα signaling via NFκ-B were significantly enriched.(Figure 1B)
We compared blood and marrow plasma by IP/IB. ApoJ is associated with light chains (LC) in blood and ApoE is not, while in +MA marrow plasma ApoJ and ApoE are strongly associated with TMCC2 and LC.
Conclusions Erythropoietic activity is increased in +MA marrows. TMCC2, an anti-apoptotic regulator of erythropoiesis, may also be a chaperone protein.  MA+ marrows enable study of the impact of amyloid on the microenvironment.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Raymond Comenzo, MD, Tufts Medical Center, Boston, MA

**Main Body of the Abstract**
**Background** Twenty percent of AL patients have marrow interstitial amyloid._ _[_Am J Clin Pathol_ **120** (2003)]. We asked how the non-plasma cell marrow cells (CD138- MC) respond to amyloid.
**Materials & Methods** We compared CD138- MC from marrows with (+MA) and without (-MA) interstitial amyloid by gene expression profiling (GEP) and single-cell RNA-sequencing (scRNA-seq) and performed qPCR, immunoprecipitation (IP) and immunoblot (IB) for selected genes or proteins.
**Results** On review of biopsies of 49 AL patients, 22 were +MA and 27 –MA; 13 +MA and 16 –MA patients were newly diagnosed. The rest were in follow up.
GEP (+MA=3, -MA=3) showed no difference among genes for proteolytic enzymes or apolipoproteins between the groups. +MA cases had significantly up-regulated erythroid genes, including transmembrane and coiled-coil domain family 2 (_TMCC2_) as seen in the Volcano plot.(Figure 1A)  PCR confirmed the high expression of TMCC2.
With the scRNA-seq (+MA=4, -MA=4) comparison, in +MA marrows CD14+ monocytes and erythroid-megakaryocyte progenitors were increased and granulocyte-monocyte progenitors decreased by 66%. By gene enrichment studies in +MA marrows pathways for TNFα signaling via NFκ-B were significantly enriched.(Figure 1B)
We compared blood and marrow plasma by IP/IB. ApoJ is associated with light chains (LC) in blood and ApoE is not, while in +MA marrow plasma ApoJ and ApoE are strongly associated with TMCC2 and LC.
**Conclusions** Erythropoietic activity is increased in +MA marrows. TMCC2, an anti-apoptotic regulator of erythropoiesis, may also be a chaperone protein.  MA+ marrows enable study of the impact of amyloid on the microenvironment.



Bone Marrow Interstitial Amyloid and Its Microenvironment PA22 (#54)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.