{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:11:24Z","timestamp":1770703884838,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":4262,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1994,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To determine whether the ALL (acute lymphoblastic leukemia) CDR3 (third complementarity\u2010determining region) repertoire represents the recombination repertoire, or shows evidence of selectional processes inherent to normal B cell differentiation or malignant transformation, we analyzed 68 ALL CDR3 regions and included 127 previously published sequences in the analyses. We found no evidence of selection prior to malignant transformation as recombination was random with 1\/3 \u201cin frame\u201d and 2\/3 \u201cout of frame\u201d joinings and usage of all three D reading frames was observed. D and J<jats:sub>H<\/jats:sub> gene segments were predominantly umutated which allowed a detailed analysis of gene usage and rearrangement characteristics. J<jats:sub>H<\/jats:sub><jats:sup>4<\/jats:sup> and J<jats:sub>H<\/jats:sub><jats:sup>6<\/jats:sup> usage (both 32.2%) was significantly different (<jats:italic>p<\/jats:italic> = 0.005) from that observed in peripheral B lymphocytes. D gene family usage roughly represented D gene family size with the exception of the D<jats:sub>XP<\/jats:sub> and D<jats:sub>A\/K<\/jats:sub> family which were over\u2010 and underrepresented (<jats:italic>p<\/jats:italic> = 0.05), respectively. D\u2010D fusions were found in 26.2% of CDR3 regions. If less stringent criteria were applied DIR homology was found in 40\/65 sequences, suggesting the frequent involvement of DIR gene segments in human CDR3 formation. The rearranged D genes were evenly distributed over the D locus, suggesting that D recombination is a predominantly random process, independent of physical location at the locus. Also, there was no correlation between J<jats:sub>H<\/jats:sub> gene usge and physical location of the rearranged D gene segment, which excludes a major contribution of the DJ<jats:sub>H<\/jats:sub> replacement recombination mechanism. In 36.1% of CDR3 regions N\u2010nucleotides at the DJ<jats:sub>H<\/jats:sub> junction were absent. This frequency is higher than observed for peripheral B lymphocytes. It is suggested that for a number of ALL the initial transformational event took place in early fetal life. We conclude that ALL CDR3 sequences show no evidence of selection prior to malignant transformation, nor of extensive changes subsequent to malignant transformation.<\/jats:p>","DOI":"10.1002\/eji.1830240418","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T20:12:04Z","timestamp":1172779924000},"page":"900-908","source":"Crossref","is-referenced-by-count":49,"title":["B precursor acute lymphoblastic leukemia third complementarity\u2010determining regions predominantly represent an unbiased recombination repertoire: Leukemic transformation frequently occurs in fetal life"],"prefix":"10.1002","volume":"24","author":[{"given":"Eric J.","family":"Steenbergen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Onno J. H. M.","family":"Verhagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonore F.","family":"van Leeuwen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk","family":"Behrendt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline A.","family":"Merle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mieke R.","family":"Wester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert E. G. Kr.","family":"Von Dem Borne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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