Mature T-cell Leukemia Primarily Involving Blood and Bone Marrow without TCL1 or MTCP1 Rearrangement: A Subtype of T-Prolymphocytic Leukemia or a Distinct Entity?

Abstract T-prolymphocytic leukemia (T-PLL) is a rare mature T-cell neoplasm defined by rearrangements involving TCL1 or MTCP1. Cases showing some overlapping features with T-PLL but lacking TCL1 and MTCP1 rearrangements have been rarely reported but are not well characterized. Whether these neoplasms belong within the category of T-PLL or represent a distinct entity is unknown. Here, we fully characterize 20 such cases. The median survival for this cohort was 34.7 months. Clinically, 40% of patients were diagnosed incidentally and 65% of patients presents with an indolent phase that was associated with a better survival. Leukemic cells were small to medium sized with a mature morphology. They were CD4-positive with TCRαβ subtype and maintained the expression of other pan-T antigens. A complex karyotype, 11q22.3/ATM deletion and chromosome 8q abnormalities were common, present in 70%, 45% and 35% of patients, respectively. The most common mutations involved ATM and JAK/STAT pathway genes, identified in 40% and 38% of patients, respectively. When this cohort was compared to 42 cases of prototypical T-PLL, they shared many overlapping clinicopathological features and had a similarly poor prognosis. We therefore propose that the neoplasms in this cohort are best classified as TCL1-family negative T-PLL.