Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups Journal Article
| Authors: | Shah, U. A.; Moshier, E.; Derkach, A.; Huang, Y.; Mailankody, S.; Tan, C. R.; Maclachlan, K.; Hultcrantz, M.; Korde, N.; Hassoun, H.; Thibaud, S.; Sanchez, L.; Rodriguez, C.; Richard, S.; Richter, J.; Rossi, A.; Cho, H. J.; Lesokhin, A.; Chari, A.; Usmani, S. Z.; Jagannath, S.; Parekh, S.; Gallagher, E. J. |
| Article Title: | Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups |
| Abstract: | Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms.We conducted a retrospective clinical study of 5383 patients withMMof which 15% had DM(White, 12% and Black, 25%). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (hazard ratio, 1.27; 95% confidence interval, 1.11-1.47; P < .001). This appeared to be driven by a marked difference in OS between White patientswith and without DMbut not in Black patients. In contrast, obesity was associated with better OS in Black patients but not in White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised nonobese diabetic (Rag1-/-/muscle creatinine kinase promoter expression of a human IGF1R [M] with a lysine [K] to arginine [R] pointmutation) mousemodel to evaluate themechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with in controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phosphorylated S6 ribosomal protein (Ser235/236) levels, indicating greater activation of the mammalian target of rapamycin pathway. Our study is, to our knowledge, the first to evaluate racial differences in DM prevalence and survival in MM, as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients; and to improve survival in MM, DM management cannot be ignored. © 2024 by The American Society of Hematology. |
| Keywords: | s6 kinase; adult; cancer survival; controlled study; protein phosphorylation; middle aged; major clinical study; overall survival; cancer growth; nonhuman; cancer incidence; animal tissue; disease association; multiple myeloma; serine; prevalence; animal experiment; animal model; cohort analysis; obesity; enzyme activation; tumor xenograft; retrospective study; survival time; genetic engineering; diabetes mellitus; mammalian target of rapamycin; western blotting; rag1 protein; nonobese diabetic mouse; race difference; mtor signaling; caucasian; immunocompromised patient; mouse model; human; male; female; article; black person |
| Journal Title: | Blood Advances |
| Volume: | 8 |
| Issue: | 1 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2024-01-09 |
| Start Page: | 236 |
| End Page: | 247 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2023010815 |
| PUBMED: | 37772981 |
| PROVIDER: | scopus |
| PMCID: | PMC10918423 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Urvi A. Shah -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
335Hassoun -
373Lesokhin -
235Korde -
292Mailankody -
268Hultcrantz -
198Shah -
154Maclachlan -
169Derkach -
141Tan -
325Usmani
Related MSK Work