Trisomy 11 and Partial Tandem Duplication of the MLL Gene in a Case of Infant Acute Myeloid Leukemia M0.

Trisomy 11 is uncommon in pediatric acute myeloid leukemia (AML) and molecular studies of AML with trisomy 11 in adult patients have recently revealed high incidence of partial tandem duplication (PTD) of the MLL gene. We report the first case of trisomy 11 and MLL-PTD in a 3 months old girl with AML, the immunophenotype of bone marrow aspirate documented blast cells positive for CD34, CD33, AntiHLA DR, CD117, and MPO <3%, M0 according to FAB classification. No exposure to potential mutagenic agents during pregnancy was documented. The most frequent translocations of MLL, t(4;11) and t(9;11), were investigated by RT-PCR at diagnosis and resulted negative, as well as other genetic abnormalities common in pediatric AML as inv 16, t(8;21), t(15;17), FLT-ITD, D835 mut. Otherwise, interphase FISH analysis, performed with a specific MLL probe, revealed a MLL triple signal (Fig. 1a). Moreover trisomy 11 was confirmed by FISH analysis with a centromeric probe for chromosome 11 (Fig. 1b). RT-PCR analysis revealed PTD of an internal portion of MLL and direct sequencing confirmed the in-frame fusion of exon 6 and exon 2 (Fig. 1c). The self-fused MLL has a duplicated N-terminal region that contains AT hook DNA-binding and DNA methyltransferase motifs. MLL-PTD may involve different exons, and it is known to be associated with a poor prognosis. Even if the oncogenic mechanism of MLL-PTD is not clear yet, several hypothesis suggested a role of DNA binding motifs duplication in the increase of affinity for MLL binding to a target site, or in the separation of autoregolatory domains from their sites of action. Beside its significance as a prognostic marker at diagnosis, MLL-PTD may be a target for PCR-based detection of minimal residual disease in AML patients.

Figure 1.

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Interphase FISH analysis with MLL probe revealed a MLL triple signal (a) and with a centromeric probe confirmed trisomy 11 (b). Direct sequencing confirmed the MLL PTD with in-frame fusion of exons 6 and exon 2(c).

Figure 1.

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Interphase FISH analysis with MLL probe revealed a MLL triple signal (a) and with a centromeric probe confirmed trisomy 11 (b). Direct sequencing confirmed the MLL PTD with in-frame fusion of exons 6 and exon 2(c).

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