Molecular Characterization of Complete and Incomplete Immunoglobulin Heavy Chain Gene Rearrangements in Hairy Cell Leukemia

Abstract

PurposeWe analyzed patients with hairy cell leukemia (HCL) to achieve a better understanding of the differentiation stage reached by HCL cells and to define the key role of the diversification of cell surface makers, especially CD25 expression. Patients and MethodsWe analyzed 38 previously untreated patients with HCL to characterize their complete (VDJH) and incomplete (DJH) immunoglobulin (Ig) heavy chain (IgH) rearrangements, including somatic hypermutation pattern and gene segment use. ResultsA correlation between immunophenotypic profile and molecular data was seen. All 38 cases showed monoclonal amplifications: VDJH in 97%, DJH in 42%, and both in 39%. Segments from the DH3 family were used more in complete compared with incomplete rearrangements (45% vs. 12%; P < .005). Furthermore, comparison between molecular and immunophenotypic characteristics disclosed differences in the expression of CD25 antigen; CD25– cases, a phenotype associated with HCL variant, showed complete homology to the germline in 3 of 5 cases (60%), whereas this characteristic was never observed in CD25+ cases (P < .005). Moreover, VH4-34, VH1-08, and JH3 segments appeared in 2, 1, and 2 CD25– cases, respectively, whereas they were absent in all CD25+ cases. ConclusionThese results support that HCL is a heterogeneous entity including subgroups with different molecular characteristics, which reinforces the need for additional studies with a larger number of patients to clarify the real role of gene rearrangements in HCL.