title: MLL amplification in acute myeloid leukemia.
abstract: The chromosomal alterations at 11q23 that involve the mixed-lineage leukemia gene (MLL, HTRX1, HRX, ALL1) are one of the most common cytogenetic abnormalities in acute leukemia and have been associated with a poor prognosis. Given that not all MLL alterations are seen under conventional cytogenetics or fluorescence in situ hybridization (FISH), it is very important to use molecular techniques to determine the cause of alteration. In this study, we describe two cases of AML in which FISH analysis showed a high-level 11q23 amplification, to confirm if this overexpression may be accompanied by partial tandem duplication of the MLL gene (MLL-PTD). Both patients showed complex karyotype and an unfavorable clinical course. The 11q23 region characterization included conventional cytogenetics, FISH, and comparative genomic hybridization analysis to study the expression patterns of several oncogenes located within the amplified region and detection of partial tandem duplication of the MLL gene by reverse-transcription polymerase chain reaction (RT-PCR) and sequencing. MLL-PTD were detected in the two patients. Moreover, patient 1 showed amplification of the MLL flanking region. Our data suggest that molecular methods such as RT-PCR or sequencing should be used to detect MLL alterations, and that amplification of MLL locus may be extended to its flanking region.
authors: Servicio de Hematología, Hospital Universitario La Fe, Avenida Campanar 21, Valencia 46009, Spain.
authors: Juan C
authors: JC
authors: Pajuelo-Gámez
authors: José
authors: J
authors: Cervera
authors: Zaida
authors: Z
authors: García-Casado
authors: Armando V
authors: AV
authors: Mena-Durán
authors: Ana
authors: A
authors: Valencia
authors: Eva
authors: E
authors: Barragán
authors: Esperanza
authors: E
authors: Such
authors: Pascual
authors: P
authors: Bolufer
authors: Miguel A
authors: MA
authors: Sanz
mesh_terms: D000208:Acute Disease; D000368:Aged; D000782:Aneuploidy; D001483:Base Sequence; D002871:Chromosome Banding; D002872:Chromosome Deletion; D005260:Female; D005784:Gene Amplification; D015894:Genome, Human; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods; D017422:Sequence Analysis, DNA
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase