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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3575-3583.
Prepublished online as a Blood First Edition Paper on August 2, 2005; DOI 10.1182/blood-2005-04-1511.
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NEOPLASIA
Immunoglobulin light chain repertoire in chronic lymphocytic leukemia
Kostas Stamatopoulos,
Chrysoula Belessi,
Anastasia Hadzidimitriou,
Tatjana Smilevska,
Evangelia Kalagiakou,
Katerina Hatzi,
Niki Stavroyianni,
Anastasia Athanasiadou,
Aliki Tsompanakou,
Theodora Papadaki,
Garyfallia Kokkini,
George Paterakis,
Riad Saloum,
Nikolaos Laoutaris,
Achilles Anagnostopoulos, and
Athanasios Fassas
From the Hematology Department and Hematopoietic Cell Transplantation (HCT) Unit, G. Papanicolaou Hospital, Thessaloniki, Greece; the Hematology Department, Nikea General Hospital, Piraeus, Greece; the Hemopathology Department, Evangelismos Hospital, Athens, Greece; the Hematology Department, Sismanogleion Hospital, Athens, Greece; and the Immunology Department, G. Gennimatas Hospital, Athens, Greece.
Immunoglobulin kappa (IGK) and immunoglobulin lambda (IGL) light chain repertoire was analyzed in 276 chronic lymphocytic leukemia (CLL) cases and compared with the relevant repertoires from normal, autoreactive, and neoplastic cells. Twenty-one functional IGKV genes were used in IGKV-J rearrangements of 179 kappa-CLL cases; the most frequent genes were IGKV3-20(A27), IGKV1-39/1D-39(O2/O12), IGKV1-5(L12), IGKV4-1(B3), and IGKV2-30(A17); 90 (50.3%) of 179 IGK sequences were mutated (similarity < 98%). Twenty functional IGLV genes were used in IGLV-J rearrangements of 97 lambda-CLL cases; the most frequent genes were IGLV3-21(VL2-14), IGLV2-8(VL1-2), and IGLV2-14(VL1-4); 44 of 97 IGL sequences (45.4%) were mutated. Subsets with "CLL-biased" homologous complementarity-determining region 3 (CDR3) were identified: (1) IGKV2-30-IGKJ2, 7 sequences with homologous kappa CDR3 (KCDR3), 5 of 7 associated with homologous IGHV4-34 heavy chains; (2) IGKV1-39/1D-39-IGKJ1/4, 4 unmutated sequences with homologous KCDR3, 2 of 4 associated with homologous IGHV4-39 heavy chains; (3) IGKV1-5-IGKJ1/3, 4 sequences with homologous KCDR3, 2 of 4 associated with unmutated nonhomologous IGHV4-39 heavy chains; (4) IGLV1-44-IGLJ2/3, 2 sequences with homologous lambda CDR3 (LCDR3), associated with homologous IGHV4-b heavy chains; and (5) IGLV3-21-IGLJ2/3, 9 sequences with homologous LCDR3, 3 of 9 associated with homologous IGHV3-21 heavy chains. The existence of subsets that comprise given IGKV-J/IGLV-J domains associated with IGHV-D-J domains that display homologous CDR3 provides further evidence for the role of antigen in CLL pathogenesis.
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