Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias. Identification of the t(9;11) as an indicator of long survival.
OBJECTIVE
We reviewed the cytogenetic pattern of the malignant cells in 36 patients who were < 20 years of age and who had M4 and M5 leukemias, excluding M4Eo cases with inv(16). We performed fluorescence in situ hybridization (FISH) and molecular studies to determine the actual incidence of 11q23/MLL abnormalities in these patients.


RESULTS
Eighteen patients had 11q23 translocations or insertions detected by cytogenetic analysis (15 cases) or by FISH (3 cases); 10 patients had t(9;11), all of whom had M5a. Eight patients had other 11q23 translocations or insertions not involving chromosome 9[t(11q23)] (four each had M4 or M5 leukemias). Eighteen cases with M4/M5 did not have 11q23 abnormalities. MLL rearrangements were found in all patients with translocations or insertions of 11q23 who were studied. Clinically, children with t(9;11) were indistinguishable from other patients with M4-M5 leukemias. In contrast, the t(11q23) group was characterized by extreme hyperleukocytosis, CNS disease, and skin involvement. Patients with the t(9;11) had a better outcome when compared with patients in the t(11q23) group (EFS +/- SE at 3 years, 56 +/- 17% versus 10 +/- 10%, p = 0.04), and to all the remaining children with M4-M5 leukemias (p = 0.04).


CONCLUSIONS
The combination of cytogenetic, FISH, and molecular analysis provides a highly sensitive strategy for detection of 11q23/MLL gene rearrangements in childhood M4-M5 leukemias. Our more precise classification of these patients allows a more accurate correlation with outcome. The favorable prognostic significance of the t(9;11) should be confirmed in prospective studies including a larger number of children as well as adults.
Martinez-Climent
J A
JA
Department of Medicine, University of Chicago Medical Center, IL 60637, USA.
Espinosa
R
R
Thirman
M J
MJ
Le Beau
M M
MM
Rowley
J D
JD
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002880:Chromosomes, Human, Pair 11; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D016019:Survival Analysis; D014157:Transcription Factors; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase