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Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23)

  • Oncogenomics
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Abstract

We showed that the LAF4 gene on 2q11.2–12 was fused to the MLL gene on 11q23 in a pediatric patient with CD10 positive acute lymphoblastic leukemia (ALL) having t(2;11)(q11;q23). The LAF4 gene, which encodes a lymphoid nuclear protein of 1227 amino acids with transactivation potential, is thought to have a role in early lymphoid development. The LAF4 protein was homologous to AF4 and AF5q31 proteins that are fused to MLL in infant early pre-B ALL and the breakpoint of LAF4 was located within the region homologous to the transactivation domain of AF4 and AF5q31. Expression of the 8.5-kb LAF4 transcript was detected in the adult heart, brain, and placenta and in the fetal brain. LAF4 expression was found to be higher in ALL cell lines than in AML and Epstein–Barr virus-transformed B-lymphocyte cell lines. These findings suggest that LAF4, AF4 and AF5q31 might define a new family particularly involved in the pathogenesis of 11q23-associated ALL.

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Abbreviations

AML:

acute myeloid leukemia

ALL:

acute lymphoblastic leukemia

RT–PCR:

reverse transcription–polymerase chain reaction

EBV-B:

EBV-transformed B lymphocyte

FISH:

fluorescence in situ hybridization

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Acknowledgements

We express our appreciation to Shoko Sohma, Hisae Soga, Yumiko Taketani (University of Tokyo) and Yukiko Konno (Dokkyo University School of Medicine) for technical assistance. We also thank Dr Kanji Sugita (Department of Pediatrics, Yamanashi University School of Medicine, Yamanashi, Japan) for providing ALL (KOCL-33, 44, 45) cell lines, and Dr Yoshinobu Matsuo (Hayashibara Biochemical Laboratories, Inc., Fujisaki Cell Center, Okayama, Japan) for providing varieties of ALL cell lines.

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Correspondence to Yasuhide Hayashi.

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Supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan, a Grant-in-Aid for Scientific Research on Priority Areas, and Uehara Memorial Foundation Grant-in-Aid for Scientific Research (B) and (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Hiwatari, M., Taki, T., Taketani, T. et al. Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23). Oncogene 22, 2851–2855 (2003). https://doi.org/10.1038/sj.onc.1206389

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