Open Access
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: 10.1055/s-0044-1788236
Abstract

Unraveling Coagulopathy in Acute Promyelocytic Leukemia: Insights from Single-Cell RNA Sequencing

Akash Maity
1   Hasan Lab, ACTREC Tata Memorial Centre, Mumbai, Maharashtra, India
2   Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Sarita Poonia
3   Department of Computational Biology and Computer Science, Indraprastha Institute of Information Technology (IIIT), New Delhi, India
,
Namrata Bhattacharya
3   Department of Computational Biology and Computer Science, Indraprastha Institute of Information Technology (IIIT), New Delhi, India
,
Hasmukh Jain
4   Department of Medical Oncology, Adult Hematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, Maharashtra, India
,
Manju Sengar
4   Department of Medical Oncology, Adult Hematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, Maharashtra, India
,
Debarka Sengupta
3   Department of Computational Biology and Computer Science, Indraprastha Institute of Information Technology (IIIT), New Delhi, India
,
Syed K Hasan
1   Hasan Lab, ACTREC Tata Memorial Centre, Mumbai, Maharashtra, India
2   Homi Bhabha National Institute, Mumbai, Maharashtra, India
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    *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.


     

    Die Autoren geben an, dass kein Interessenkonflikt besteht.

    Publikationsverlauf

    Artikel online veröffentlicht:
    08. Juli 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/)

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