Page 229 - Haematologica Vol. 107 - September 2022

LETTER TO THE EDITOR ABCD
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Figure 2. Isoproterenol and propranolol regulate multiple myeloma sensitivity to the proteasome inhibitor bortezomib. (A) Model of how b adrenergic signaling establishes a tumor promoting triad between multiple myeloma (MM) and the skewed common myeloid lineage specification in the BM (bone marrow) niche. (B) ADRB2 expression in MM gene expression subtypes from the CoMMpass study (IA17). CD-1: Cyclin D1; LB: low bone disease; MS: MMSET; CD-2: Cyclin D1 and CD20; PR: proliferation; HP: hyperdiploid; MF: MAF. (C) ADRB2 expression in patients with t(14;20) (IGH-MAFB) (D) and t(14;16) (IGH-MAF) translocations. P- values were determined by two-sided t-test. (E) MM lines treated with dose range of propranolol (PRO) for 24 hours (h) assessed for viability using Annexin V/DAPI flow cytometric staining. (F) Cell lines treated with 75 mM PRO or isoproterenol (ISO) as indicated for 24 h assessed for viability using Annexin V/DAPI flow cytometric staining. (G) MM patient BM mononuclear cells treated with 50 or 100 mM PRO in combination with bortezomib (BTZ) assessed for BTZ half maximal inhibitory concentration (I.C.50) using AnnexinV/DAPI flow cytometric staining.
effects of b agonist-stimulated elevation in GMP and lastly; iii) propranolol regulates MAFB/GATA1 expression to restore MEP commitment in MM (Figure 2A).
Ectopic MAFB expression in mouse HSC promotes ac- quisition of a tumoral plasma cell fate without induction of MAF in tumor cells.12 MAF also has a role in promoting MM growth and its expression correlates with poor OS.13 MAF thus has both cell extrinsic and intrinsic roles in
shaping myeloma genesis, warranting development of strategies to target MAF for MM therapy. Evaluation of RNA sequencing in primary MM samples from the CoMMpass trial14 (clinical trials gov. Identifier: NCT0145429) indicated ADRB2 was significantly higher in the MAF (MF) gene ex- pression subtype (Figure 2B). Consistent with this, ADRB2 expression was elevated in MM samples harboring the high risk-associated t(14;20) or t(14;16) translocations that
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