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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 1066-1068
Novel SH3 protein encoded by the AF3p21 gene
is fused to the mixed lineage leukemia protein in a therapy-related
leukemia with t(3;11) (p21;q23)
Kimihiko Sano,
Akira Hayakawa,
Jin-Hua Piao,
Yoshiyuki Kosaka, and
Hajime Nakamura
From the Department of Pediatrics, Kobe University School of
Medicine, Kobe, Japan.
The mixed lineage leukemia (MLL) gene located at
chromosome band 11q23 is frequently rearranged in patients with
therapy-related acute monocytic leukemia who received topoisomerase II
inhibitors. We have identified a novel fusion partner of MLL
(FAB M5b) in a patient who developed t-AML 9 years after
treatment for acute lymphoblastic leukemia (ALL). The leukemic cells
had a sole karyotypic abnormality of t(3;11) (p21;q23). Screening of a
genomic DNA library, prepared from leukemic cell DNA, identified
rearranged clones composed of MLL and a novel gene on
chromosome 3p21 (AF3p21). The AF3p21 gene
encodes a protein of 722 amino acids, which contains an Src homology 3 (SH3) domain, a proline-rich domain, and a bipartite nuclear localizing
signal (NLS). RNA analysis demonstrated that exon 6 of the MLL
gene fused to exon 2 of the AF3p21 gene. The resulting chimeric
protein consists of AT-hooks, methyltransferase, and
transcription repressor domains of MLL in addition to the AF3p21
proline-rich domain and NLS but not the AF3p21 SH3 domain.
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