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

AbstractWe 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 VHDJH rearranged allele in most cases. We investigated if Sμ deletions were related to VH 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 VH 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 VHDJH rearranged alleles suggests a possible role in the stabilization of the isotype of the expressed immunoglobulin