Leukemia Research 24 (1999) 73 – 77 Case report Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions Hajime Okita a , Akihiro Umezawa a, *, Mariko Fukuma a , Takashi Ando a , Fumihiko Urano a , Makoto Sano a , Yuji Nakata a,b , Taijiro Mori c , Jun-ichi Hata a a Department of Pathology, Keio Uniersity School of Medicine, 35 Shinanomachi, Shinjuku -ku, Tokyo 160 -8582, Japan b Department of Pediatrics, Keio Uniersity School of Medicine, 35 Shinanomachi, Shinjuku -ku, Tokyo 160 -8582, Japan c Department of Pediatrics, Social Insurance Saitama Chuo Hospital, Urawa, Japan Received 19 March 1999; accepted 28 June 1999 Abstract Jumping translocations (JTs) are unbalanced chromosomal translocations in which an identical chromosomal region is translocated to the telomeric region of different chromosomes. JTs are rare in hematological malignancies where they are second translocations and may be an indicator of poor prognosis. We report a case of acute myeloid leukemia with t(16;21) and a JT in which the long arm of chromosome 1 distal to q21 is translocated to the terminal region of chromosome 10. The leukemic cells exhibit high expression of EAT/mcl1, an anti-apoptotic Bcl-2 related gene. Since EAT/mcl1 is mapped to 1q21 near the breakpoint in the JTs, high level expression of EAT/mcl1 may be associated with the poor prognosis of leukemia with JTs. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: EAT/mcl1; Jumping translocation; Apoptosis; Bcl-2; Acute myeloid leukemia; TLS/FUS-ERG www.elsevier.com/locate/leukres 1. Introduction We have isolated the EAT/mcl1 gene which is up-reg- ulated at the early stage of differentiation of human embryonal carcinoma cells and murine embryonic stem cells [1,2]. EAT/mcl1 was originally identified as a gene whose expression is induced during myeloid leukemia cell differentiation by the phorbol ester TPA [3]. EAT/ mcl1 is a Bcl-2 related gene, and overexpression confers resistance to apoptosis under some apoptosis-inducing conditions including chemotherapeutic agents in vitro [4,5]. Elevated expression of Bcl-2, the prototype of this gene family is associated with resistance to chemothera- peutic drugs [6]. Bcl-2 is involved in t(14;18) chromoso- mal translocations commonly found in follicular lymphoma and is considered to be responsible for accumulation of the lymphoma cells. Jumping translocations (JTs) are unbalanced chro- mosomal translocations in which an identical chromo- somal region is translocated to the terminal region of different chromosomes. In most cases, the long arm of chromosome 1 distal to q21 is translocated onto the terminal region of other chromosomes and this results in partial trisomy of 1q21-qter. JTs are rare in hemato- logical malignancies with only about 20 cases reported to date [7]. A JT is a poor prognostic indicator since it is found in advanced disease, and the tumor cells with a JT are resistant to chemotherapeutic agents [8,9]. Here we report a case of acute myeloid leukemia with a JT which shows high expression of EAT/mcl1. These results taken together with other information suggest a possible function for EAT/mcl1 in AML with a JT. Abbreiations: AML, acute myeloid leukemia; cDNA, complemen- tary DNA; JT, jumping translocation. * Corresponding author. Fax: +81-3-3353-3290. E-mail address: au@med.keio.ac.jp (A. Umezawa) 0145-2126/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII:S0145-2126(99)00137-X