guest ::
| Home > Publications database > Laminin Receptor Characterization in Acute Myeloid Leukemia: Integrin α7β1 Defines leukemic cells with Migratory Potential. |
| Home > Publications database > Laminin Receptor Characterization in Acute Myeloid Leukemia: Integrin α7β1 Defines leukemic cells with Migratory Potential. |
| Journal Article | DKFZ-2025-03065 |
; ; ; ; ; ; ; ; ; ; ; ; ;
2025
Elsevier Science
Amsterdam [u.a.]
Abstract: Interactions with the bone marrow (BM) niche are crucial for promoting self-renewal and survival of acute myeloid leukemia (AML) cells. Consequently, AML cells express a variety of surface receptors to engage with BM niche cells and extracellular matrix proteins, including laminins. Despite the association of laminin receptors with stemness in healthy hematopoiesis, their role in AML remains poorly understood. In this study, we present a comprehensive examination of the laminin receptors integrin α3β1, α6β1, α7β1 and basal cell adhesion molecule (BCAM) in AML. We demonstrate that high mRNA expression of all four laminin receptors correlates with poor overall survival. Notably, integrin α6 and α7 display the highest cell surface density among the examined laminin receptors and are higher expressed on AML cells compared to healthy controls. Moreover, our results indicate that the absence of integrin α7 expression can identify cells with increased colony forming potential, even in patients that are negative for the stem cell marker CD34 usually used to enrich LSC. Re-analyzing survival data from the TCGA-AML cohort, integrin α7 expression further allows refinement of the risk stratification based on the LSC score where low LSC and integrin α7 levels confer superior survival. Lastly, integrin α7 appears to mark leukemic cells with enhanced migratory potential, which can be inhibited by the anti-integrin α7 blocking antibody in vitro and in vivo. Together, our results confirm the association of high laminin receptor expression with poor prognosis, and establish integrin α7 as marker of high migratory leukemic cells. TEASER ABSTRACT: Acute myeloid leukemia (AML) cells engage with supportive bone marrow niche cells and extracellular matrix (ECM) proteins through surface receptors. Here, we demonstrate that high mRNA expression of the laminin receptors integrin α3β1, α6β1, α7β1 and BCAM correlates with poor overall survival. Moreover, integrin α7 expression marks leukemic cells displaying enhanced migratory potential. Together, we believe that our study significantly advances our understanding of AML-ECM interactions, and provides important insights that might be instrumental in the development of future therapies addressing therapy resistance in AML.
Keyword(s): acute myeloid leukemia ; bone marrow niche ; integrin α7β1 ; laminin receptors ; leukemic stem cells ; migration and homing
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz
; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
