High frequency of fusion transcripts of exon 11 and exon 4/5 in AF-4 gene is observed in cord blood, as well as leukemic cells from infant leukemia patients with t(4;11)(q21;q23)

• Published in: Leukemia Vol. 12; no. 9; pp. 1398 - 1403
• Main Authors: YAMAMOTO, S, ZAITSU, M, ISHII, E, YATSUKI, H, MIZUTANI, S, EGUCHI, M, IHARA, K, OKAMURA, T, HARA, T, MIYAZAKI, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.09.1998; Nature Publishing Group
• Subjects: AF-4 gene; Biological and medical sciences; Blood; Chromosome 11; Chromosome 4; Chromosomes; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 4; Cord blood; Exons - genetics; Fetal Blood; Fetuses; Fibroblasts; Hematologic and hematopoietic diseases; Humans; Infant, Newborn; Infants; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukemogenesis; Medical sciences; MLL protein; Myeloid-Lymphoid Leukemia Protein; Neoplasm Proteins - analysis; Neoplasm Proteins - blood; Oncogene Proteins, Fusion - analysis; Oncogene Proteins, Fusion - blood; Peripheral blood; Polymerase Chain Reaction; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; RNA, Messenger - analysis; Translocation; Translocation, Genetic; Chromosomal aberration; Human; Acute; Infant; Malignant hemopathy; Blood; Messenger RNA; Abnormal chromosome B4; Lymphoproliferative syndrome; Gene rearrangement; Cytogenetics; Abnormal chromosome; Genetics; Umbilical cord; Acute lymphocytic leukemia; Abnormal chromosome C11; Hybrid gene; Chromosome translocation
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2401135

The MLL gene located on chromosome 11q23 and its translocation to the AF-4 gene located on chromosome 4q21 play a pivotal role in leukemogenesis in infancy. Studies of identical leukemic twins have provided evidence of the MLL rearrangement as a fetal event during pregnancy. We analyzed the presence and frequency of the MLL/AF-4 rearrangement in normal cord blood. Although no chimeric mRNA of MLL or AF-4 was detected in 65 cord blood samples, in-frame fusion transcripts of exon 11 and exon 4 or 5 of the AF-4 gene were detected in three of the samples by a nested polymerase chain reaction. When primers of exon 11 and exon 5 of the AF-4 gene were used, two forms of fusion transcripts (AF-4 exon 11/4 or exon 11/5) were detected in 20 of the 65 cord blood samples (31%) and also four of six leukemic cell samples with t(4;11) (67%), whereas such transcripts were not observed in any of 21 peripheral blood samples nor in fetal fibroblasts. These findings suggest that the in-frame fusion of exon 11 and exon 4 or 5 of the AF-4 gene frequently occurs in hematopoietic cells during the intrauterine period, even in a healthy fetus. Although it is unknown whether the proteins of the AF-4 fusion transcripts have some functions, the instability of the AF-4 gene may be associated with the leukemogenesis of infant leukemia.