MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13.
Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic abnormality seen in acute monocytic leukemia. We also isolated a normal MLLT3 cDNA and found an open reading frame encoding at least 318 amino acids with high serine/proline content (24.8%). The chimeric mRNAs were demonstrated to be fused to MLL in frame, as found in t(11;19) and t(4;11) leukemias. The predicted MLLT3 protein demonstrated a significant homology to that of the MLLT1 gene at 19p13 involved in t(11;19) leukemia. The highest homology, up to 74.1%, was found in 86 amino acids of the C-terminus, suggesting that this region is of particular importance for leukemogenesis in t(9;11) leukemia. Northern blot analysis with the MLLT3 cDNA probe against normal tissues revealed multiple transcripts in lymphoid organs. A survey of hematopoietic cell lines demonstrated relatively stronger signals in cells belonging to megakaryocytic and erythroid lineages. As previously found in t(11;19) leukemia, heterogeneous MLL-MLLT3 chimeric mRNAs could be detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) in t(9;11) leukemia samples.
Iida
S
S
Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Nagoya, Japan.
Seto
M
M
Yamamoto
K
K
Komatsu
H
H
Tojo
A
A
Asano
S
S
Kamada
N
N
Ariyoshi
Y
Y
Takahashi
T
T
Ueda
R
R
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D002899:Chromosomes, Human, Pair 9; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D009687:Nuclear Proteins; D009857:Oncogenes; D011392:Proline / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012694:Serine / Q000032:analysis; D014157:Transcription Factors; D014178:Translocation, Genetic
D018076:DNA, Complementary; C081448:MLLT1 protein, human; C489901:MLLT3 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D012694:Serine; D011392:Proline