Most immunoglobulin heavy chain switch mu rearrangements in B‐cell chronic lymphocytic leukemia are internal deletions

FEBS Letters

Menard, Sylvie¹  Balsari, Andrea¹  Capello, Daniela²  Nardini, Elena¹  Vitolo, Umberto³  Gaidano, Gianluca²  Rizzi, Simona¹ 

[1] Department of Experimental Oncology, Molecular Targeting Unit, National Cancer Institute, Via Venezian 1, 20133 Milan, Italy;Division of Internal Medicine, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;Division of Hematology, A.O. San Giovanni Battista della Citta’ di Torino, Turin, Italy

关键词: B-cell chronic lymphocytic leukemia;    Isotype switch;    Somatic hypermutation;    Sμ;    switch mu region;    VH;    variable heavy chain gene;    JH;    joining heavy chain region;   

DOI  :  10.1016/S0014-5793(02)02672-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We investigated 38 cases of B-cell chronic lymphocytic leukemia (B-CLL) for the presence of non-productive rearrangements in the Sμ regions and defined for the first time the molecular nature of these rearrangements. Southern blot analysis revealed Sμ region rearrangements in 13 cases (34%) and polymerase chain reactions (PCRs) indicated that these rearrangements consisted of internal deletions of the Sμ region. Long-distance PCRs localized the Sμ deletions in the V_HDJ_H rearranged allele in most cases. We investigated if Sμ deletions were related to V_H somatic mutations that, together with isotype switch recombination, are indicative of the B-cell maturation stage. No significant correlation between the presence of Sμ deletions and V_H somatic mutations was found, indicating that the two processes are independent in B-CLL. Moreover no significant correlation between Sμ deletions and prognosis was observed. Having shown that Sμ internal deletions are not chromosome translocations rules out their involvement in the onset of malignancy, while their localization in the V_HDJ_H rearranged alleles suggests a possible role in the stabilization of the isotype of the expressed immunoglobulin.

【 授权许可】

Unknown