MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies of 11q23.
We here report the clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data on 14 patients with a myeloid malignancy and structural aberration of chromosome band 11q23 associated with overrepresentation or amplification of the MLL gene. The number of copies of MLL varied from three (two cases) to a cluster consisting of multiple hybridization spots. Together with previous reports, available data indicate that amplification of 11q23/MLL is a recurrent genetic change in myeloid malignancy. It affects mainly elderly patients and is often associated with dysplastic bone marrow changes or with complex karyotypic aberrations, suggestive of genotoxic exposure. It is associated with a poor prognosis. In addition, FISH analysis of nine cases with additional 11q probes showed that the overrepresented chromosomal region is generally not restricted to MLL, and Southern blot analysis indicated that amplification does not involve a rearranged copy of this gene. The significance of MLL amplification and the mechanisms by which it could play a role in leukemogenesis and/or disease progression remain to be elucidated.
Center for Human Genetics, University of Leuven, Leuven, Belgium.
L
L
Michaux
I
I
Wlodarska
M
M
Stul
J
J
Dierlamm
F
F
Mugneret
C
C
Herens
B
B
Beverloo
A
A
Verhest
C
C
Verellen-Dumoulin
G
G
Verhoef
D
D
Selleslag
V
V
Madoe
M
M
Lecomte
B
B
Deprijck
A
A
Ferrant
A
A
Delannoy
S
S
Marichal
C
C
Duhem
M
M
Dicato
A
A
Hagemeijer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D018628:Gene Dosage; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D012189:Retrospective Studies; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase