Single-cell RNA sequencing coupled to TCR profiling of large granular lymphocyte leukemia T cells

Shouguo Gao (), Zhijie Wu, Bradley Arnold, Carrie Diamond, Sai Batchu, Valentina Giudice, Lemlem Alemu, Diego Quinones Raffo, Xingmin Feng, Sachiko Kajigaya, John Barrett, Sawa Ito and Neal S. Young
Additional contact information
Shouguo Gao: National Institutes of Health
Zhijie Wu: National Institutes of Health
Bradley Arnold: National Institutes of Health
Carrie Diamond: National Institutes of Health
Sai Batchu: National Institutes of Health
Valentina Giudice: National Institutes of Health
Lemlem Alemu: National Institutes of Health
Diego Quinones Raffo: National Institutes of Health
Xingmin Feng: National Institutes of Health
Sachiko Kajigaya: National Institutes of Health
John Barrett: National Institutes of Health
Sawa Ito: University of Pittsburgh
Neal S. Young: National Institutes of Health

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract T-cell large granular lymphocyte leukemia (T-LGLL) is a lymphoproliferative disease and bone marrow failure syndrome which responds to immunosuppressive therapies. We show single-cell TCR coupled with RNA sequencing of CD3+ T cells from 13 patients, sampled before and after alemtuzumab treatments. Effector memory T cells and loss of T cell receptor (TCR) repertoire diversity are prevalent in T-LGLL. Shared TCRA and TCRB clonotypes are absent. Deregulation of cell survival and apoptosis gene programs, and marked downregulation of apoptosis genes in CD8+ clones, are prominent features of T-LGLL cells. Apoptosis genes are upregulated after alemtuzumab treatment, especially in responders than non-responders; baseline expression levels of apoptosis genes are predictive of hematologic response. Alemtuzumab does not attenuate TCR clonality, and TCR diversity is further skewed after treatment. Inferences made from analysis of single cell data inform understanding of the pathophysiologic mechanisms of clonal expansion and persistence in T-LGLL.

Date: 2022
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DOI: 10.1038/s41467-022-29175-x

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