LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia.
Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot analysis. Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.2-q12 as a fusion partner of the MLL gene. The LAF4 gene was identified previously by its high sequence homology to the AF4 protein and encodes a protein of 1,227 amino acids. The t(4;11)(q21;q23), creating the MLL-AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with an extremely poor prognosis. Our findings further suggest that fusion of MLL to one of the AF4 family members (AF4/LAF4/AF5Q31) might determine a proB-cell phenotype in infant leukemia.
von Bergh
Anne R M
AR
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Beverloo
H Berna
HB
Rombout
Paul
P
van Wering
Elisabeth R
ER
van Weel
Margreet H
MH
Beverstock
Geoffrey C
GC
Kluin
Philip M
PM
Slater
Rosalyn M
RM
Schuuring
Ed
E
D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011519:Proto-Oncogenes; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D014178:Translocation, Genetic / Q000235:genetics
C097738:AFF3 protein, human; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C467122:MLL-LAF4 fusion protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D011495:Histone-Lysine N-Methyltransferase