Multilineage lymphoid clonal hematopoiesis: a cross-sectional, correlative analysis of plasma cell dyscrasias and large granular lymphocytic leukemia
6 affiliations
- 1Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH USA
- 2Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, University of Murcia, IMIB-Pascual Parrilla, CIBERER—Instituto de Salud Carlos III, Murcia, Spain
- 3Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
- 4Division of Hematology, Department of Internal Medicine, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH USA
- 5Department of Internal Medicine, The Ohio State University, Columbus, OH USA
- 6Robert J. Tomsich Department of Pathology and Laboratory Medicine, Diagnostic Institute, Cleveland Clinic, Cleveland, OH USA
Abstract
Clonal expansions in large granular lymphocytic leukemia (LGLL) may arise in response to immune dysregulation in the context of other hematologic malignancies. This study aimed to investigate the co-occurrence of LGLL and plasma cell dyscrasias (PCDs) to assess its prevalence, features, and potential underlying mechanisms. We conducted a cross-sectional study involving 2064 PCD cases and 534 LGLL cases. Of the 534 LGLL cases, 20% co-occurred with PCD, while LGLL was present in 2% of the 2064 PCD cases. Among 117 patients with both conditions, PCDs were predominantly associated with IgM M-protein, while LGLL patients had increased NK-cell proliferation and fewer mutations in STAT3/5B. The co-occurrence was linked to a higher incidence of autoimmune conditions, B-cell neoplasms, and more severe immune-mediated cytopenias. In symptomatic PCD/LGLL patients with low plasma-cell infiltration, B-cell-targeted therapies outperformed immunosuppression, suggesting humoral involvement. Correlation with biological parameters revealed elevated interleukin-6 and inhibitory effects of sera of symptomatic PCD/LGLL patients on hematopoietic cells. Our findings suggest an association between PCD and LGLL, characterized by distinct features that may have significant implications for clinical management. These results highlight the importance of considering hematologic co-occurrences in clinical practice and warrant further investigation into the molecular mechanisms linking these conditions.
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BibTeX
@article{bravoperez2026multilineage,
title = {{Multilineage lymphoid clonal hematopoiesis: a cross-sectional, correlative analysis of plasma cell dyscrasias and large granular lymphocytic leukemia}},
author = {Carlos Bravo-Perez and Carmelo Gurnari and Arda Durmaz and Miguel Ruiz and Zachary Braunstein and Naomi Kawashima and Justin Jiang and Zachary Brady and Atsushi Marumo and Arooj Ahmed and Mark Orland and Aashray Mandala and Luca Guarnera and Matteo D’Addona and Serhan Unlu and Christopher Haddad and Kartik Lakhotiya and Praveena Thiagarajan and Megan Nakashima and Heesun J. Rogers and Jonathan E. Brammer and Valeria Visconte and Jaroslaw P. Maciejewski},
journal = {Leukemia},
year = {2026},
month = aug,
doi = {10.1038/s41375-026-03071-5},
url = {https://doi.org/10.1038/s41375-026-03071-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multilineage lymphoid clonal hematopoiesis: a cross-sectional, correlative analysis of plasma cell dyscrasias and large granular lymphocytic leukemia
AU - Carlos Bravo-Perez
AU - Carmelo Gurnari
AU - Arda Durmaz
AU - Miguel Ruiz
AU - Zachary Braunstein
AU - Naomi Kawashima
AU - Justin Jiang
AU - Zachary Brady
AU - Atsushi Marumo
AU - Arooj Ahmed
AU - Mark Orland
AU - Aashray Mandala
AU - Luca Guarnera
AU - Matteo D’Addona
AU - Serhan Unlu
AU - Christopher Haddad
AU - Kartik Lakhotiya
AU - Praveena Thiagarajan
AU - Megan Nakashima
AU - Heesun J. Rogers
AU - Jonathan E. Brammer
AU - Valeria Visconte
AU - Jaroslaw P. Maciejewski
PY - 2026
DA - 2026/08/05
JO - Leukemia
DO - 10.1038/s41375-026-03071-5
UR - https://doi.org/10.1038/s41375-026-03071-5
AB - Clonal expansions in large granular lymphocytic leukemia (LGLL) may arise in response to immune dysregulation in the context of other hematologic malignancies. This study aimed to investigate the co-occurrence of LGLL and plasma cell dyscrasias (PCDs) to assess its prevalence, features, and potential underlying mechanisms. We conducted a cross-sectional study involving 2064 PCD cases and 534 LGLL cases. Of the 534 LGLL cases, 20% co-occurred with PCD, while LGLL was present in 2% of the 2064 PCD cases. Among 117 patients with both conditions, PCDs were predominantly associated with IgM M-protein, while LGLL patients had increased NK-cell proliferation and fewer mutations in STAT3/5B. The co-occurrence was linked to a higher incidence of autoimmune conditions, B-cell neoplasms, and more severe immune-mediated cytopenias. In symptomatic PCD/LGLL patients with low plasma-cell infiltration, B-cell-targeted therapies outperformed immunosuppression, suggesting humoral involvement. Correlation with biological parameters revealed elevated interleukin-6 and inhibitory effects of sera of symptomatic PCD/LGLL patients on hematopoietic cells. Our findings suggest an association between PCD and LGLL, characterized by distinct features that may have significant implications for clinical management. These results highlight the importance of considering hematologic co-occurrences in clinical practice and warrant further investigation into the molecular mechanisms linking these conditions.
SN - 0887-6924
SN - 1476-5551
ER -