Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).
We showed that the LAF4 gene on 2q11.2-12 was fused to the MLL gene on 11q23 in a pediatric patient with CD10 positive acute lymphoblastic leukemia (ALL) having t(2;11)(q11;q23). The LAF4 gene, which encodes a lymphoid nuclear protein of 1227 amino acids with transactivation potential, is thought to have a role in early lymphoid development. The LAF4 protein was homologous to AF4 and AF5q31 proteins that are fused to MLL in infant early pre-B ALL and the breakpoint of LAF4 was located within the region homologous to the transactivation domain of AF4 and AF5q31. Expression of the 8.5-kb LAF4 transcript was detected in the adult heart, brain, and placenta and in the fetal brain. LAF4 expression was found to be higher in ALL cell lines than in AML and Epstein-Barr virus-transformed B-lymphocyte cell lines. These findings suggest that LAF4, AF4 and AF5q31 might define a new family particularly involved in the pathogenesis of 11q23-associated ALL.
Department of Pediatrics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Mitsuteru
M
Hiwatari
Tomohiko
T
Taki
Takeshi
T
Taketani
Masafumi
M
Taniwaki
Kenichi
K
Sugita
Mayuko
M
Okuya
Mitsuoki
M
Eguchi
Kohmei
K
Ida
Yasuhide
Y
Hayashi
D019677:Artificial Gene Fusion; D001483:Base Sequence; D002675:Child, Preschool; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002889:Chromosomes, Human, Pair 2; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051788:Myeloid-Lymphoid Leukemia Protein; D015260:Neprilysin / Q000032:analysis; D009687:Nuclear Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011519:Proto-Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors; D014178:Translocation, Genetic; D016335:Zinc Fingers
C097738:AFF3 protein, human; D017931:DNA Primers; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D011495:Histone-Lysine N-Methyltransferase; D015260:Neprilysin