21. A case of acute myeloid leukemia with gain of two copies of neocentromeric chromosome 11

Abstract

Neocentromeres are ectopic centromeres that arise on a chromosome at a location that is normally not centromeric [1]. Since the discovery of the first human neocentromere in 1993, more than 90 cases of constitutional supernumerary marker chromosomes containing neocentromeres have been documented. However, neocentromere formation has only been observed in three tumor categories including lipomatous tumors, lung carcinoma and acute myeloid leukemia (AML) [2]. In AML, neocentromeric chromosomes have been described in three cases: a derivative r(8) [3], inv dup(10q) [4] and neo(1)[5]. Here we report a neocentromeric chromosome 11 in a 76 year-old female with AML. Chromosome analysis of unstimulated peripheral blood revealed an abnormal clone with two extra copies of a neocentromeric chromosome 11: 48,XX,+11,+11,iso(11)(qter->q22->neo->q22->q13::q13->qter)x2[19]/46,XX[1]. FISH analysis using an α-satellite probe specific for centromere 11 and locus specific probe for 11q23 (MLL locus) indicated that these two neocentromeres do not have the genomic sequence of centromere 11. This abnormal clone has four copies of chromosome 11: two structurally normal chromosomes 11 and two structurally abnormal neocentromeric chromosomes 11. In sum, this leads to a total of six copies of 11q. Partial gain of chromosome 11q, containing the unrearranged mixed lineage leukaemia (MLL) gene is a rare but recurrent anomaly in myeloid malignancies. However, gain of 11q in the form of a neocentromeric chromosome 11 has not been described previously. Further study on the interaction between kinetochore protein and this active neocentromere will provide evidence about the mechanism of a functional neocentromere formation.