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Heterogeneity of VH-JH gene rearrangement patterns: an insight into the biology of B cell precursor ALL

Lookup NU author(s): Professor Christine Harrison FRCPath FMedSci


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Oligoclonal B cell proliferation, as defined by the presence of more than one leukemic clone, has been detected in approximately 20% to 30% of patients with acute lymphoblastic leukemia (ALL) using PCR or Southern blotting. An accurate assessment of these populations is required to avoid false negative measurements of minimal residual disease (MRD) in follow-up bone marrow (BM) samples of ALL patients. In this study, we analysed 29 ALL patients with two or more immunoglobulin heavy (IGH) chain gene rearrangements in the presentation samples using IGH fingerprinting PCR and sequence analysis. Thirty-nine (51%) of 76 sequences (from 15 patients), shared no VNDNJ homology (ie different CDR3 regions). In the remaining 14 patients, at least two related VH sequences were identified in each patient (identical DNJ sequences). Numerical abnormalities of chromosome 14 was detected in 10 patients. Eight patients were analysed at presentation and relapse. In four of them, expansion of a minor presentation-clone was detected at relapse while the major presentation clone disappeared, confirming 'subclonal evolution'. Finally, in our cohort of patients, the presence of related or unrelated IGH clones did not influence overall survival.

Publication metadata

Author(s): Moreira I, Papaioannou M, Mortuza FY, Gameiro P, Palmisano GL, Harrison CJ, Prentice HG, Mehta AB, Hoffbrand AV, Foroni L

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2001

Volume: 15

Issue: 10

Pages: 1527-1536

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group


DOI: 10.1038/sj.leu.2402234

Notes: Journal Article Research Support, Non-U.S. Gov't England official journal of the Leukemia Society of America, Leukemia Research Fund, U.K


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