MLL/SEPTIN6 chimeric transcript from inv ins(X;11 )(q24;q23q13) in acute monocytic leukemia:: Report of a case and review of the literature

Rearrangements of the MILL gene on chromosome II, band q23, are one of the most common genetic changes in acute leukemia. Reciprocal translocation is the most common form of MILL rearrangement, and the partner genes in MILL translocation are notably diverse. Involvement of the SEPTIN6 gene on Xq24 in MILL rearrangements occurs very rarely, with only six cases having been documented in the literature. Of note, the MLLISEPTIN6 rearrangements in these cases were cryptic or complex, and it was shown that the 5'-MLL/SEPTIN6-3' transcript resides on the derivative X chromosome rather than on the derivative chromosome I I as in the majority of cases of MILL translocations. These observations suggested that MILL and SEPTIN6 reside on their respective chromosome loci in reverse orientation, that is, centromere-to-telomere and telomere-to-centromere, respectively. We here report a case of acute monocytic leukemia with inv ins(X;11)(q24;q23q13) in a 29-month-old child. Fluorescence in situ hybridization study revealed the break-apart 5'-MLL segment to be translocated to the derivative X chromosome, and reverse transcriptase-polyme rase chain reaction followed by sequencing analysis confirmed the 5-MLL/SEPTIN6-3' chimeric transcript. This case is the first to provide direct cytogenetic evidence for the salient nature of the MLL/SEPTIN6 rearrangement. We reviewed clinical and cytogenetic features of all cases of 11q23 and Xq22-24 rearrangements reported up to now, including six cases where the involvement of the SEPTIN6 gene was confirmed by molecular techniques. (C) 2003 Wiley-Liss, Inc.