Molecular Distinctions Between Variant and Classic Hairy Cell Leukemia

A34 Background:10-20% of patients with hairy cell leukemia (HCL) have a variant (HCLv) and present with high tumor burden in spleen and peripheral blood, and are less responsive to purine analogs. HCLv cells lack CD25 and sometimes CD103. Differentiating HCLv from classic HCL (HCLc) is sometimes difficult and it is unclear whether HCLv and HCLc are different disorders. Detailed molecular distinctions between HCLv and HCLc have not been reported. Methods: Patients with HCL were studied by flow cytometry and PCR to sequence the monoclonal immunoglobulin heavy chain rearrangements. Differences were analyzed by Fisher’s exact and Wilcoxon non-parametric tests. Results: 50 and 21 VH-D-JH rearrangements were obtained from 49 HCLc and 19 HCLv patients, respectively. All rearrangements except 2 each for HCLc and HCLv were productive with no premature termination codons. The incidence of VH4 usage was higher in HCLv than in HCLc (57% vs 20%, p=0.0041). VH4-34 was the most common VH gene in HCLv and was more common in HCLv than in HCLc (33% vs 8%, p=0.012). The percentage of rearrangements which were unmutated (defined as