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

Oligoclonal B cell proliferation, as defined by the presence of more than o ne leukemic clone, has been detected in approximately 20% to 30% of patient s with acute lymphoblastic leukemia (ALL) using PCR or Southern blotting. A n accurate assessment of these populations is required to avoid false negat ive measurements of minimal residual disease (MRD) in follow-up bone marrow (BM) samples of ALL patients. In this study, we analysed 29 ALL patients w ith two or more immunoglobulin heavy (IGH) chain gene rearrangements in the presentation samples using IGH fingerprinting PCR and sequence analysis. T hirty-nine (51%) of 76 sequences (from 15 patients), shared no VNDNJ homolo gy (ie different CDR3 regions). In the remaining 14 patients, at least two related VH sequences were identified in each patient (identical DNJ sequenc es). 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 m ajor presentation clone disappeared, confirming 'subclonal evolution'. Fina lly, in our cohort of patients, the presence of related or unrelated IGH cl ones did not influence overall survival.