title: Skewed rearrangement of the VH4-21 gene during pre-B acute lymphoblastic leukemia.
abstract: Thirty-six pre-B acute lymphoblastic leukemias (ALL) were studied for VH family expression. Among the 35 detected rearrangements, VH1 family genes were expressed in 7, VH2 in 1, VH3 in 18, VH4 in 6 and VH6 in 3. This expression is close to that expected according to the complexity of the system. The complete sequence of the 6 VH4 genes was examined in order to determine whether there is a skewed rearrangement of individual genes in this family. Our results indicate rearrangement of VH4-21 in 3 cases, 71-4 in one, 58P2 in one case and probably of a new germinal VH4 gene for the sixth case. All the genes were displaying an almost complete homology with their germinal VH counterparts. The 6 sequenced genes associated with 6 different D gene segments displaying a close homology with their germinal counterpart. JH4 segment was expressed in 3 cases and JH6 in the remaining 3. These results associated with previous results obtained by others indicate that there is skewed rearrangement of the VH4-21 gene in pre-B ALL. It is presently unknown whether this phenomenon is the consequence of a selective process or whether it reflects what normally occurs in the normal human functional repertoire, which could be more limited than the germline repertoire.
authors.affiliation: Département d'Hématologie, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Maloum
authors.forename: C
authors.initials: C
authors.lastname: Magnac
authors.forename: O
authors.initials: O
authors.lastname: Pritsch
authors.forename: J L
authors.initials: JL
authors.lastname: Binet
authors.forename: H
authors.initials: H
authors.lastname: Merle-Béral
authors.forename: G
authors.initials: G
authors.lastname: Dighiero
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003001:Cloning, Molecular; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D016415:Sequence Alignment