[Rearrangements of the mixed lineage leukemia gene in acute myeloid leukemia].

OBJECTIVE

To study the frequency of mixed lineage leukemia (MLL) gene rearrangements in patients with acute myeloid leukemia (AML) and to determine the significance thereof.

METHODS

Conventional cytogenetics (CC) and karyotype analysis were conducted on the bone marrow cells from 58 patients with acute myelocytic leukemia (AML), 47 adults (aged 15 approximately 67) and 11 children (aged 1 approximately 14). Fluorescence in situ hybridization (FISH) using the whole chromosome painting (WCP) probes of the chromosomes 1, 5, 11, 16, 17, and 21 was performed. A total of 58 patients were included in this study. Forty-seven of these patients with AML were adults and the remaining were children. Both conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) were carried out. FISH analysis was performed utilizing commercially available DNA probes, including whole chromosome painting probes, locus specific probes, and specific and dual color/multiple color translocation fusion probes.

RESULTS

Six out of the 58 patients (10.3%) were found to have MLL gene rearrangements, either an extra signal of MLL gene or a disruption of MLL gene due to a translocation or deletion or duplication. Of these six patients with MLL gene rearrangements, four were adults and two were children. In addition to MLL gene rearrangements, complex chromosomal changes were also detected in five of these patients: 47 - 49, XX, der (1) t (1; 17) (p36.1; q23), +4, +10, der (11) t (11; 17) (q23; q23), -17, -18, +20, +21?. ish +21 (wcp21+), der (1) t (1; 17) (wcp17+), der (11) t (11; 17) (wcp11+; wcp17+); 46, XX, del (5) (q13q33), r (11) (p15q25), +r (11) (p15q25). ishr (11) (wcp11+, MLL+), +r (11) (wcp11+, MLL+); 46, XY, del (11) (q23) [2]/46, idem, add (16) (p13.1) [8]/46, XY [10]. ishadd (16) (wcp16+), rea (11) (wcp11+); 55, XY, + markers, ish 11q23 (MLL x 3), +21 (wcp21+); and 46, XY, add (11) (q23) [6]/46, idem, t (15; 17) (q22; q21) [12]/46, XY [2]. ish dup (11) (MLL++), t (15; 17) (PML+, RARa+; RARa-) [24].

CONCLUSION

MLL gene rearrangement is relatively common in AML patients. Because MLL gene arrangements due to translocation or other structural changes are associated with poor response to chemotherapy and poor prognosis, routine testing for this gene rearrangement should be provided to all newly diagnosed patients with AML.