The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related acute myeloid leukemia with t(8;19)(p11;q13).
The monocytic leukemia zinc finger protein KAT6A (formerly MOZ) gene is recurrently rearranged by chromosomal translocations in acute myeloid leukemia (AML). KAT6A is known to be fused to several genes, all of which have histone acetyltransferase (HAT) activity and interact with a number of transcription factors as a transcriptional coactivator. The present study shows that the leucine twenty homeobox (LEUTX) gene on 19q13 is fused to the KAT6A gene on 8p11 in a therapy-related AML with t(8;19)(p11;q13) using the cDNA bubble PCR method. The fusion transcripts contained 83 nucleotides upstream of the first ATG of LEUTX and are presumed to create in-frame fusion proteins. LEUTX is known to have a homeobox domain. Expression of the LEUTX gene was only detected in placenta RNA by RT-PCR, but not in any tissues by Northern blot analysis. The putative LEUTX protein does not contain any HAT domain, and this is the first study to report that KAT6A can fuse to the homeobox gene. The current study, with identification of a new partner gene to KAT6A in a therapy-related AML, does not elucidate the mechanisms of leukemogenesis in KAT6A-related AML but describes a new gene with a different putative function.
Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
Yoshiaki
Y
Chinen
Tomohiko
T
Taki
Yasuhiko
Y
Tsutsumi
Satoru
S
Kobayashi
Yosuke
Y
Matsumoto
Natsumi
N
Sakamoto
Junya
J
Kuroda
Shigeo
S
Horiike
Kazuhiro
K
Nishida
Hirofumi
H
Ohno
Naokuni
N
Uike
Masafumi
M
Taniwaki
D000595:Amino Acid Sequence; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D017809:Fatal Outcome; D050939:Gene Fusion; D005801:Genes, Homeobox; D051548:Histone Acetyltransferases / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D008969:Molecular Sequence Data; D014178:Translocation, Genetic
D018398:Homeodomain Proteins; C000590731:LEUTX protein, human; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human