High prevalence and immunophenotypic diversity of clonal T‑large granular lymphocytes in JAK2‑mutated myeloproliferative neoplasms

Patients with JAK2‑mutated MPN may develop clonal T‑cell expansions, but the prevalence, immunophenotypic spectrum, and association with other lymphoid clones remain poorly defined. Clonal T‑large granular lymphocyte (T‑LGL) expansions have been observed in myeloproliferative neoplasms (MPN), but systematic data comparing different MPN driver mutations are lacking. This retrospective study of 354 MPN patients (182 BCR::ABL⁺, 163 JAK2⁺, 9 CALR⁺) evaluated the prevalence and immunophenotypic features of clonal T‑LGL, and examined their co‑occurrence with monoclonal B cells and plasma cells. We retrospectively analyzed flow cytometry and molecular data from 354 consecutive MPN patients between January 2021 and April 2026. Clonal T‑LGL were identified by T-cell receptor beta chain constant region 1 (TRBC1) restriction ( > 85% or < 15%) with LGL phenotype (CD3⁺CD57⁺ or CD3⁺CD56⁺). Clonal burden, CD4/CD8 subset, CD5/CD7 expression, CD56/CD57 positivity, and coexisting monoclonal B or plasma cells were analyzed. Clonal T‑LGL were detected in 34 of 354 MPN patients (overall detection rate 9.6%). Detection rates were 17.2% (28/163) in JAK2⁺ patients, 3.3% (6/182) in BCR::ABL⁺ patients, and 0 in CALR⁺ patients (JAK2⁺ vs. BCR::ABL⁺: χ² = 18.45, P < 0.001). Among the 28 JAK2⁺ cases, CD8⁺ T‑LGL accounted for 71.4% (20/28), CD4⁺ for 14.3% (4/28), CD4^-CD8^-for 10.7% (3/28), and TCRγδ⁺ for 3.6% (1/28). TRBC1‑restriction showed decreased expression ( < 15%) in 60.7% (17/28) and increased ( > 85%) in 39.3% (11/28). CD5 downregulation/loss was observed in 57.1% (16/28) and CD7 downregulation/loss in 46.4% (13/28). CD56/CD57 positivity were 35.7% (10/28) and 78.6% (22/28), respectively. Notably, the majority of CD8⁺ T-LGL clones also expressed CD57, representing the predominant immunophenotype. In the JAK2⁺ group, 2 patients (7.1%) had concurrent monoclonal B cells. JAK2‑mutated MPN patients have a significantly higher prevalence of clonal T‑LGL (17.2%) compared with BCR::ABL⁺ MPN (3.3%) with diverse immunophenotypes, predominantly CD8⁺ with frequent CD57 expression and CD5/CD7 aberrancy. A small subset of JAK2⁺ T-LGL patients (2/28, 7.1%) had concurrent monoclonal B cells, no plasma cell clones were identified. Routine TRBC1‑based flow cytometric screening for T‑cell clonality is recommended in JAK2‑mutated MPN patients.