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Dissecting the cell of origin of aberrant SALL4 expression in myelodysplastic syndrome
Dissecting the cell of origin of aberrant SALL4 expression in myelodysplastic syndrome
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Length:
20 minutes
Released:
Dec 5, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.12.05.518121v1?rss=1
Authors: Tatetsu, H., Watanabe, M., Liu, J., Tokunaga, K., Iwanaga, E., Komohara, Y., Thrash, E., Matsuoka, M., Tenen, D. G., Chai, L.
Abstract:
Myelodysplastic syndrome (MDS) is a group of heterogeneous diseases characterized by cytologic dysplasia and cytopenias resulting from ineffective hematopoiesis. Oncofetal protein SALL4 is a known oncogene in MDS and its baseline expression level serves as a prognostic biomarker for MDS at the time of diagnosis. In addition, a recent study showed that SALL4 upregulation following hypomethylating agent treatment in MDS patients correlates with poor outcomes. Despite its important mechanistic and diagnostic significance, the cellular identity of bone marrow cells with aberrant SALL4 expression in MDS patients remains unknown. In this study, we analyzed MDS bone marrow cells on single cell level by mass cytometry (CyTOF) and found that SALL4 was mainly aberrantly expressed in the hematopoietic stem and progenitor cells (HSPC) as well as myeloid lineages. Within the HSPC population from MDS patients, SALL4 and p53 were co-expressed, with the highest co-expressing clones harboring pathogenic TP53 mutations. Overall, our study characterizes for the first time the aberrant SALL4 expression in primary MDS patient samples at a single-cell level. Further studies on the SALL4/p53 network for in-depth mechanistic investigation are needed in the future.
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Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2022.12.05.518121v1?rss=1
Authors: Tatetsu, H., Watanabe, M., Liu, J., Tokunaga, K., Iwanaga, E., Komohara, Y., Thrash, E., Matsuoka, M., Tenen, D. G., Chai, L.
Abstract:
Myelodysplastic syndrome (MDS) is a group of heterogeneous diseases characterized by cytologic dysplasia and cytopenias resulting from ineffective hematopoiesis. Oncofetal protein SALL4 is a known oncogene in MDS and its baseline expression level serves as a prognostic biomarker for MDS at the time of diagnosis. In addition, a recent study showed that SALL4 upregulation following hypomethylating agent treatment in MDS patients correlates with poor outcomes. Despite its important mechanistic and diagnostic significance, the cellular identity of bone marrow cells with aberrant SALL4 expression in MDS patients remains unknown. In this study, we analyzed MDS bone marrow cells on single cell level by mass cytometry (CyTOF) and found that SALL4 was mainly aberrantly expressed in the hematopoietic stem and progenitor cells (HSPC) as well as myeloid lineages. Within the HSPC population from MDS patients, SALL4 and p53 were co-expressed, with the highest co-expressing clones harboring pathogenic TP53 mutations. Overall, our study characterizes for the first time the aberrant SALL4 expression in primary MDS patient samples at a single-cell level. Further studies on the SALL4/p53 network for in-depth mechanistic investigation are needed in the future.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Dec 5, 2022
Format:
Podcast episode
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