Previous studies have shown that B-ALL relapse is often driven by relapse-specific chemoresistance mutations in loci such as the NT5C2 nucleotidase gene,49, 50 or mutations in genes like SETD2, CREBBP and others, which can be present at diagnosis or gained at relapse.48, 51 We propose that the persistence of small B-ALL clones, defined by their unique BCR sequence, is a surrogate for partial inherent chemoresistance and/or inadequate initial therapy. The gene discussed is BCR; the disease is acute lymphoblastic leukemia.