Genetic Abnormality in T-Cell Large Granular Lymphocyte Leukemia – Single Nucleotide Polymorphism Array Study of 30 Cases.
Weifen Zeng, Christine L O'Keefe, Michael Clemente, Jaroslaw P Maciejewski, Eric Hsi. Cleveland Clinic, OH
Background: The genetic aberration associated with T-cell large granular lymphocyte leukemia (T-LGLL)is poorly understood based on few literature with very limited case number studied. Single nucleotide polymorphism array (SNP-A) is a method for whole genome scanning by combining genotyping (classification of a homozygous or heterozygous constellation at a polymorphic locus) and copy number analysis (intensity of hybridization signal). This study is the first SNP array study on a relatively large number (30 cases) of T-LGLL.
Design: 30 cases (15 female and 15 male) of T-LGLL, diagnosed from 1986-2007, were included in this study. Peripheral blood smears were reviewed for evaluation of LGL count. Monoclonality was confirmed in all cases by T-cell receptor (TCR) Vb FCI and TCRg rearrangement. Genome-Wide Human SNP 6.0 Arrays were used per the manufacturer's instructions. Signal intensity was analyzed and SNP calls determined using Gene Chip Genotyping Analysis Software Version (4.0) (GTYPE). Data were analyzed using Genotyping Console v2.1 software (Affymetrix). Lesions identified by SNP-A were compared with the Database of Genomic Variants (http://projects.tcag.ca/variation/) and with an internal control series (N=554) to identify and exclude known copy number variants (CNVs). A genomic abnormality (GA) was defined as: 1) gain or loss >1Mb, 2) UPD >25Mb or 3) more than 3 UPDs detected in the same patient.
Results: Median age was 61.5 years at diagnosis (range, 17 to 78 years). 3 patients (10%) were asymptomatic while the rest had anemia, neutropenia, thrombocytopenia, or bi- or pan-cytopenia. 9 patients (30%) had GA detected by SNP array. The number of aberrancy (GA) ranged from 1 to 8 per patient, including uniparental disomy (UPD). While no specific GA was detected, chromosome 3, 6, 14 and 21 had the largest sizes of changes (>25Mb). Among the 9 patients, none were asymptomatic. The detection of GA was not correlated with LGL count (P>0.05).
Conclusions: T-LGLL is a heterogenous group of disease. While specific genetic abnormalities were not detected, some T-LGLL cases demonstrated GA suggesting genetic instability that is associated with symptomatic disease. This supports the concept that some, but not all, cases are truly neoplastic rather than simply clonal immune proliferations of genetically normal cells. However, further studies in larger numbers of cases may help identify GA that might be pathogenetically important.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 233, Tuesday Morning