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Acute lymphoblastic leukemia (ALL) can be preceded by a prodromal phase of bone marrow failure. In serial trephine biopsies in a girl with acquired bone marrow hypoplasia, we have identified a monoclonal B-cell precursor population characterized by a clone-specific IgH-FR3 gene rearrangement. Progression to ALL more than 4 months later was accompanied by acquisition of an additional T-cell receptor rearrangement. Thus, hypoplastic pre- and overt leukemia share a common clonal origin. Prospective biobanking and extended molecular analysis can help to better understand the nature and sequence of genetic events during progression of a covert (pre)leukemic clone. Pediatr Blood Cancer 2011;56:301-303. © 2010 Wiley-Liss, Inc.