[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].


CONCLUSIONS
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.
Zhang
Li-jun
LJ
Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Lu
Xiang-lan
XL
He
Juan
J
Li
Yan
Y
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D000091402:Prohibitins
C000717331:PHB2 protein, human; D000091402:Prohibitins; D051788:Myeloid-Lymphoid Leukemia Protein