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The t(4;9)(q11;q33) fuses CEP110 to KIT in a case of acute myeloid leukemia

Leukemia volume 25, pages 1049–1050 (2011)Cite this article

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KIT is a class III receptor tyrosine kinase (RTK) that has an important role in hemopoiesis, particularly with regard to stem cell maintenance and mast cell development.1 KIT is normally activated by engagement with its ligand, stem cell factor, but a variety of acquired KIT point mutations have been described in acute myeloid leukemia (AML) and systemic mastocytosis that result in constitutive, ligand-independent activation.1 In contrast to other related RTKs such as PDGFRA, PDGFRB and FLT3, constitutive activation of KIT by gene fusion has not been described.2, 3

We previously identified a 25-year-old man with AML (FAB M1) and a novel translocation that was initially described as a t(4;9)(q13;q34) by standard cytogenetic analysis but was subsequently revised to t(4;9)(q11;q33) following spectral karyotyping. The presence of BCR-ABL and DEK-CAN mRNA transcripts were both excluded by RT-PCR analysis.4 To characterize the translocation in more detail, we initially performed split-apart interphase fluorescence in situ hybridization (FISH) analysis for genes that are known to be translocation targets in myeloid neoplasia. No rearrangements were seen with probes that flanked ABL at 9q34 or PDGFRA at 4q12;5 however, split signals (not shown) were seen with bacterial artificial chromosome (BAC) clones RP11-525G7 and RP11-477J21 that were selected to flank CEP110, a gene encoding a centrosomal protein that is fused to FGFR1 in the 8p11 myeloproliferative syndrome with a t(8;9)(p12;q33).6 Hypothesizing that the fusion partner was likely to be a tyrosine kinase, we next performed split apart FISH for the two other RTKs located at 4q12. No rearrangement was seen for KDR, but split signals were seen for KIT using BACs RP11-80L11 and RP11-273B19 (not shown).

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Authors and Affiliations

  1. University of Southampton, Wessex Regional Genetics Laboratory, Salisbury, UK

    F H Grand, K Waghorn, T Ernst & N C P Cross

  2. The First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan

    K Ohyashiki

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  1. F H Grand
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  2. K Waghorn
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  3. T Ernst
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  4. K Ohyashiki
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  5. N C P Cross
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Correspondence to F H Grand.

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Grand, F., Waghorn, K., Ernst, T. et al. The t(4;9)(q11;q33) fuses CEP110 to KIT in a case of acute myeloid leukemia. Leukemia 25, 1049–1050 (2011). https://doi.org/10.1038/leu.2011.40

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