January 2001, Volume 15, Issue 1, Pages 121 - 127

Original Manuscript

Immunoglobulin lambda isotype gene rearrangements in B cell malignancies T Tümkaya1, M van der Burg1, R Garcia Sanz2, M Gonzalez Diaz2, AW Langerak1, JF San Miguel2 & JJM van Dongen1 1Department of Immunology, Erasmus University Rotterdam/University Hospital Rotterdam, Rotterdam, The Netherlands     2Department of Hematology, Hospital Clinico Universitario, Salamanca, Spain     Correspondence to: Prof JJM van Dongen, MD, PhD, Dept of Immunology, Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Fax: 31 10 4089456

Keywords

immunoglobulin lambda genes;   B cell malignancies;   Southern blot analysis;   immunoglobulin lambda isotypes

Abstract

The human immunoglobulin lambda (IGL) locus contains seven J-C gene regions of which only J-C1, J-C2 J-C3 and J-C7 encode the four Ig isotypes, ie Mcg, Ke-Oz-, Ke-Oz+, and Mcp, respectively. We used isotype-specific DNA probes for detection of IGL gene rearrangements in 212 B cell malignancies: 76 precursor B cell acute lymphoblastic leukemias (precursor B-ALL), 74 Ig+ chronic B cell leukemias (CBL), 34 Ig+ non-Hodgkin lymphomas (B-NHL), and 28 Ig+ multiple myelomas (MM). The J-C3 gene region was most frequently involved (50%), followed by J-C2 (38%) and J-C1 (9%). There was no involvement of the J-C4 and J-C5 gene regions. Rearrangements to J-C6 (n = 4) were exclusively found in precursor B-ALL (19% of all IGL rearrangements in precursor B-ALL) and only a single J-C7 recombination was detected in an Ig+ B-NHL. In the group of Ig+ malignancies, a significant shift was observed from predominant J-C3 usage (54%) in mature surface Ig+ malignancies (CBL and B-NHL) to 60% J-C2 usage in Ig+ secreting MM. The distribution of IGL isotype rearrangements found in MM resembled the Ig isotype protein expression reported in MM patients. Based on these extensive Southern blot data, we suggest that a rapid and efficient detection of clonal IGL gene rearrangements can be obtained when a single BglII digest is used in combination with the IGLJ2 probe, which detects clonality in >95% of cases with an Ig+ malignancy. Higher percentages (>98%) can be reached by including a second digest (HindIII) that reduces the chance of comigration of rearranged and germline bands. In case of precursor B-ALL we recommend including the IGLJ6 probe for the detection of rearrangements to J-C6. Leukemia (2001) 15, 121-127.

Received 5 June 2000; Accepted 6 September 2000

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