PMID- 14654972 OWN - NLM STAT- MEDLINE DCOM- 20040316 LR - 20190816 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 13 IP - 1 DP - 2004 Jan TI - Increased amplification proximal to the MLL gene in acute myeloid leukemia. PG - 63-7 AB - Amplification of the chromosomal region 11q23 encompassing the MLL gene has been observed in patients with acute myeloid leukemia (AML). Patients with this abnormality often have a poor response to chemotherapy and short survival. We have studied the regions flanking the MLL gene using 8 bacterial artificial chromosome (BAC) probes and dual color fluorescence in situ hybridization (FISH) analysis. Two contigs of BAC probes flanking the MLL gene, were constructed by standard primer walking and BAC end sequencing. For comparison, metaphase chromosome preparations were also hybridized with a commercial MLL specific probe. Metaphase chromosomes were prepared from the bone marrow sample of an 80-year old female patient with AML-M1 and the cytogenetic aberration der(11)hsr(11) (q23). FISH analysis on metaphase chromosomes showed amplification on the homogeneously staining region (hsr) and marker chromosomes for both the MLL gene and the BAC probes. Using dual color FISH, probes proximal to MLL showed greater amplification than those distal to MLL, as represented by additional red signals on both metaphase and interphase chromosomes. Ratios of the copy numbers of the BAC probes relative to the chromosome 11 centromere copy number confirmed a higher copy number for probes proximal to MLL. These results suggest that other gene(s) proximal to MLL could be the target gene(s) of amplification in this case and not the MLL gene as previously assumed. FAU - Lee, Ann Siew-Gek AU - Lee AS AD - Division of Medical Sciences, National Cancer Centre, Singapore 169610. dmslsg@nccs.com.sg FAU - Lie, Daniel Khun-Hong AU - Lie DK FAU - Tien, Sim-Leng AU - Tien SL FAU - Rudduck-Sivaswaren, Christina AU - Rudduck-Sivaswaren C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (DNA-Binding Proteins) RN - 0 (KMT2A protein, human) RN - 0 (Transcription Factors) RN - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) SB - IM MH - Acute Disease MH - Aged MH - Aged, 80 and over MH - Chromosome Aberrations MH - Chromosomes, Human, Pair 11 MH - DNA-Binding Proteins/*genetics MH - Female MH - *Gene Amplification MH - Histone-Lysine N-Methyltransferase MH - Humans MH - In Situ Hybridization, Fluorescence MH - Leukemia, Myeloid/*genetics MH - Myeloid-Lymphoid Leukemia Protein MH - *Proto-Oncogenes MH - *Transcription Factors EDAT- 2003/12/05 05:00 MHDA- 2004/03/17 05:00 CRDT- 2003/12/05 05:00 PHST- 2003/12/05 05:00 [pubmed] PHST- 2004/03/17 05:00 [medline] PHST- 2003/12/05 05:00 [entrez] PST - ppublish SO - Int J Mol Med. 2004 Jan;13(1):63-7.