73. Chromosomal microarray-based genomic profiling of T-cell Large Granular Lymphocyte Leukemia

Abstract

Jinbo Fan, Lei Wang, Eli Williams

University of Virginia, Charlottesville, VA, USA

T-cell large granular lymphocyte (T-LGL) leukemia is a rare lymphoproliferative disorder characterized by infiltration of blood and bone marrow with large granular lymphocytes, splenomegaly, and cytopenias. Most patients with T-LGL leukemia follow an indolent course, with a median survival of over 10 years. However, a subset of T-LGL leukemia cases exhibits more aggressive clinical behavior. Recent identification of recurrent activating STAT3 gene mutations in T-LGL leukemia suggests that sequence alterations play a role in the persistence of clonal T-cell expansions. However, cytogenetic alterations have rarely been reported in T-LGL leukemia. Here we present the chromosomal microarray analysis (CMA) of twenty T-LGL leukemia cases, which represents the largest cohort to date. All cases were analyzed by the CytoScan HD chromosomal microarray. Detected alterations were classified based on the published ACMG/CGC guidelines. Copy number abnormalities and copy neutral loss of heterozygosity were detected in seven T-LGL leukemia cases (7/20, 35%), with few recurrent CNAs identified, indicating extensive genetic heterogeneity. The most common copy-number abnormality was a gain of 1p36, and the most common copy-neutral abnormality was a loss of heterozygosity of 17q12q25. Data from this pilot study demonstrates that a subset of T-LGL leukemia cases carry recurrent cytogenetic alterations. Follow-up CMA testing of additional cases is currently underway to clarify the contribution of recurrent cytogenetic alterations to the pathogenesis of T-LGL leukemia. Additionally, correlation of the cytogenetic alterations profile with the clinical course may provide prognostic insight into the existence of aggressive or transformed variants of T-LGL leukemia.