Unraveling Coagulopathy in Acute Promyelocytic Leukemia: Insights from Single-Cell RNA Sequencing
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788236
*Corresponding author: (e-mail: syedhasanbio@yahoo.com/shasan@actrec.gov.in).
Abstract
Background: APL is a blood cancer, caused by t(15:17) chromosomal translocation, leading to the accumulation of abnormal promyelocytes in the marrow. Coagulopathy (abnormal bleeding) is a significant challenge in APL treatment, and its molecular mechanisms are unclear. We studied single-cell multiome sequencing to uncover the molecular pathogenesis of coagulopathy in APL.
Materials and Methods: We analyzed abnormal promyelocytes from two APL patients, experiencing severe bleeding and no bleeding, and CD34+ cells from a healthy donor sequencing scRNA and scATAC libraries. The data were processed and analyzed using Cell Ranger ARC pipeline and distinct cell populations were characterized using Seurat pipeline in R programming.
Results: ScRNA-seq data analysis revealed that abnormal promyelocytes have significant cellular and gene expression diversity. Coagulopathy-associated unique cell cluster was identified with basic Seurat analyses. Further, cell type annotation has revealed that the unique cell population exhibits a leukemic stem cell (LSC) signature, while the control group displays a hematopoietic stem cell (HSC) signature. This distinction has been confirmed by the unique expression of LSC marker genes (CD96, IL1RAP, and IL3RA) and HSC marker genes (CD34, CRHBP, NPR3). It is worth mentioning that coagulopathy-related genes (ANXA2 and TF/F3) were exclusively upregulated in LSCs, implying the involvement of LSCs in coagulopathy.
Conclusion: Early data indicate that coagulopathy in APL may be regulated by a specific subpopulation of leukemic cells, rather than a general disruption of leukemic cells. By examining these particular cells and their regulatory pathways in a larger cohort sample, we may uncover potential therapeutic targets for treating APL-associated coagulopathy.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: syedhasanbio@yahoo.com/shasan@actrec.gov.in).
Abstract
Background: APL is a blood cancer, caused by t(15:17) chromosomal translocation, leading to the accumulation of abnormal promyelocytes in the marrow. Coagulopathy (abnormal bleeding) is a significant challenge in APL treatment, and its molecular mechanisms are unclear. We studied single-cell multiome sequencing to uncover the molecular pathogenesis of coagulopathy in APL.
Materials and Methods: We analyzed abnormal promyelocytes from two APL patients, experiencing severe bleeding and no bleeding, and CD34+ cells from a healthy donor sequencing scRNA and scATAC libraries. The data were processed and analyzed using Cell Ranger ARC pipeline and distinct cell populations were characterized using Seurat pipeline in R programming.
Results: ScRNA-seq data analysis revealed that abnormal promyelocytes have significant cellular and gene expression diversity. Coagulopathy-associated unique cell cluster was identified with basic Seurat analyses. Further, cell type annotation has revealed that the unique cell population exhibits a leukemic stem cell (LSC) signature, while the control group displays a hematopoietic stem cell (HSC) signature. This distinction has been confirmed by the unique expression of LSC marker genes (CD96, IL1RAP, and IL3RA) and HSC marker genes (CD34, CRHBP, NPR3). It is worth mentioning that coagulopathy-related genes (ANXA2 and TF/F3) were exclusively upregulated in LSCs, implying the involvement of LSCs in coagulopathy.
Conclusion: Early data indicate that coagulopathy in APL may be regulated by a specific subpopulation of leukemic cells, rather than a general disruption of leukemic cells. By examining these particular cells and their regulatory pathways in a larger cohort sample, we may uncover potential therapeutic targets for treating APL-associated coagulopathy.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India