Immunoglobulin lambda isotype gene rearrangements in B cell malignancies

The human immunoglobulin lambda (IGL) locus contains seven J-C lambda gene regions of which only J-C lambda1, J-C lambda2 J-C lambda3 and J-C lambda7 encode the four Ig lambda isotypes, ie Mcg, Ke(-)Oz(-), Ke(-)Oz(+), and Mcp , respectively. We used isotype-specific DNA probes for detection of IGL ge ne rearrangements in 212 B cell malignancies: 76 precursor B cell acute lym phoblastic leukemias (precursor B-ALL), 74 Ig lambda (+) chronic B cell leu kemias (CBL), 34 Ig lambda (+) non-Hodgkin lymphomas (B-NHL), and 28 Ig lam bda (+) multiple myelomas (MM), The J-C lambda3 gene region was most freque ntly involved (50%), followed by J-C lambda2 (38%) and J-C lambda1 (9%), Th ere was no involvement of the J-C lambda4 and J-C lambda5 gene regions. Rea rrangements to J-C lambda6 (n=4) were exclusively found in precursor B-ALL (19% of all IGL rearrangements in precursor B-ALL) and only a single J-C la mbda7 recombination was detected in an Ig lambda (+) B-NHL. In the group of Ig lambda (+) malignancies, a significant shift was observed from predomin ant J-C lambda3 usage (54%) in mature surface Ig lambda (+) malignancies (C BL and B-NHL) to 60% J-C lambda2 usage in Ig lambda (+) secreting MM. The d istribution of IGL isotype rearrangements found in MM resembled the Ig lamb da isotype protein expression reported in MM patients. Based on these exten sive Southern blot data, we suggest that a rapid and efficient detection of clonal IGL gene rearrangements can be obtained when a single Bg Lambda1 di gest is used in combination with the IGLJ2 probe, which detects clonality i n >95% of cases with an Ig lambda (+) malignancy. Higher percentages (>98%) can be reached by including a second digest (HindIII) that reduces the cha nce of comigration of rearranged and germline bands. In case of precursor B -ALL we recommend including the IGLJ6 probe for the detection of rearrangem ents to J-C lambda6.