Characteristics of immunoglobulin heavy chain variable region genes in childhood B-cell acute lymphoblastic leukemia / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the origin of childhood B-cell acute lymphoblastic leukemia (B-ALL) and its epitopes recognized by cytotoxic T lymphocytes (CTL) in immunoglobulin heavy chain variable region (IgHV).</p><p><b>METHODS</b>Seven IgHV gene families were respectively amplified by PCR and directly sequenced in 108 childhood ALL. The amino acid sequences were deducted from sequenced nucleotides. Bioinformatics was applied to analyses of recombination patterns, somatic mutations and germline gene segments usage, and to prediction of epitopes recognized by CTL.</p><p><b>RESULTS</b>IgHV gene rearrangements were identified in 66% of the cases, including 37 (52.1%) monoallelic rearrangements, 26 (36.6%) biallelic rearrangements and 8 (11.3%) oligoclonal rearrangements. Among the obtained 40 B-ALL IgHV gene sequences, 8 (20.0%) were in frame rearrangements without stop codons. V(H3) (11/40), V(H4) (11/40) and V(H1) (8/40) amounted to 75% rearranged V(H) families. V(H)(4-59) and V(H)(4-34) were the most frequently rearranged V(H)(4) family gene segments. Usage of D2 and D3 families was most prominent (35.9% and 28.2%, respectively). Increased frequency of D7-27 (15.4%) was found as compared to that of normal peripheral B lymphocytes (P = 0.02). J(H)(6) was found in 47.5% rearrangements followed by J(H)(4) (27.5%). 8/40 (20.0%) DJ(H) junctions lacked N nucleotides, which was higher than that reported for normal peripheral B lymphocytes (P = 0.02). 17.5% B-ALL IgHV contained scattered replacement mutations with replacement (R) to silent (S) substitution ratio (R/S ratio) <or= 1 in complementarity determining region (CDR). Above 80% potential HLA class I molecule-binding peptides were derived from framework regions of immunoglobulin heavy chains in 26 B-ALL cases and 1 - 2 peptides of the same IgHV family were shared by B-ALL.</p><p><b>CONCLUSION</b>B-ALL originated from progenitor or precursor B lymphocytes. B-ALL IgHV genes are of germline characteristics. Potential T cell epitopes were derived from framework regions 1 and 3 of immunoglobulin heavy chain in B-ALL.</p>