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  • Title: Normal and pathological V(D)J recombination: contribution to the understanding of human lymphoid malignancies.
    Author: Dadi S, Le Noir S, Asnafi V, Beldjord K, Macintyre EA.
    Journal: Adv Exp Med Biol; 2009; 650():180-94. PubMed ID: 19731811.
    Abstract:
    The majority of haematological cancers involve the lymphoid system. They include acute lymphoblastic leukemias (ALL), which are arrested at variable stages of development and present with blood and bone marrow involvement and chronic leukemias, lymphomas and myelomas, which present with infiltration of a large variety of hematopoietic and non hematopoietic tissues by mature lymphoid cells which express a surface antigen receptor. The majority involve the B-cell lineage and the vast majority have undergone clonal rearrangement of their Ig and/or TCR rearrangements. Analysis of Ig/TCR genomic V(D)J repertoires by PCR based lymphoid clonality analysis within a diagnostic setting allows distinction of clonal from reactive lymphoproliferative disorders, clonal tracking for evidence of tumor dissemination and follow-up, identification of a lymphoid origin in undiagnosed tumors and evaluation of clonal evolution. Ig/TCR VDJ errors are also at the origin of recombinase mediated deregulated expression of a variety of proto-oncogenes in ALL, whereas in lymphoma it is increasingly clear that IgH containing translocations result from abnormalities other than VDJ errors (somatic hypermutation and/or isotype switching). In addition to this mechanistic contribution to lymphoid oncogenesis, it is possible that failure to successfully complete expression of an appropriate Ig or TCR may lead to maturation arrest in a lymphoid precursor, which may in itself contribute to altered tissue homeostasis, particularly if the arrest occurs at a stage of cellular expansion.
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