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Activation of a novel palmitoyltransferase ZDHHC14 in acute biphenotypic leukemia and subsets of acute myeloid leukemia

Leukemia volume 25, pages 367–371 (2011)Cite this article

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The current World Health Organization (WHO) classification of hematological malignancies includes a number of entities defined by specific genetic abnormalities. Most known abnormalities result from chromosomal translocations and mutations involving genes encoding transcription factors or tyrosine kinases. We report here the finding of activation of a novel palmitoyltransferase ZDHHC14 through the chromosomal translocation t(6;14)(q25;q32) in patients with acute biphenotypic leukemia.

Biphenotypic leukemia refers to a single population of leukemic blasts co-expressing antigens of both lymphoid and myeloid lineages. It is difficult to diagnose, with no specific genetic lesion identified as a diagnostic marker. It is also difficult to treat, as many cases are resistant to chemotherapy. Based on the lineage specificity of co-expressed antigens, biphenotypic leukemia can be further classified into B/myeloid and T/myeloid. Although the molecular basis of biphenotypic leukemia is largely unknown, a recurrent chromosomal translocation, t(6;14)(q25;q32), has been documented in biphenotypic leukemia in two children1, 2 and two adults.3 This translocation has not been characterized at the molecular level. We recently identified this same chromosomal translocation in two additional individuals with T/myeloid leukemia. The first patient was a 17-year-old boy diagnosed with T/myeloid leukemia based on co-expression of the T-cell markers CD2, cytoplasmic CD3 (cCD3) and CD7, and the myeloid markers CD13 and CD117, as well as CD38 and HLA-DR. Initial karyotype analysis indicated an abnormality involving 6q. Subsequent fluorescence in-situ hybridization (FISH) analysis revealed a t(6;14)(q25;q32). The second patient was an 11-year-old boy with T/myeloid leukemia co-expressing CD2, cCD3, CD7, CD13, CD33, CD34, CD58 and CD117. To look for subtle loss or gain of genomic fragments at the translocation breakpoints or elsewhere in the genome, we scanned the genomes of both patients using an array-based comparative genomic hybridization platform, the Agilent 244 K whole-genome array chip (http://www.agilent.com/chem/goCGH). Although polymorphic copy number variations previously identified in healthy individuals (database of genomic variants) were observed in each patient, no consistent genomic imbalance was detected. Special attention was given to the translocation breakpoints, but no significant gain or loss of DNA was appreciated in either patient. Thus, the t(6;14) was genomically balanced in both patients.

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References

  1. Hayashi Y, Pui CH, Behm FG, Fuchs AH, Raimondi SC, Kitchingman GR et al. 14q32 translocations are associated with mixed-lineage expression in childhood acute leukemia. Blood 1990; 76: 150–156.

    CAS  Google Scholar 

  2. Batanian JR, Dunphy CH, Gale G, Havlioglu N . Is t(6;14) a non-random translocation in childhood acute mixed lineage leukemia? Cancer Genet Cytogenet 1996; 90: 29–32.

    Article  CAS  Google Scholar 

  3. Georgy M, Yonescu R, Griffin CA, Batista DA . Acute mixed lineage leukemia and a t(6;14)(q25;q32) in two adults. Cancer Genet Cytogenet 2008; 185: 28–31.

    Article  CAS  Google Scholar 

  4. Su XY, Della-Valle V, Andre-Schmutz I, Lemercier C, Radford-Weiss I, Ballerini P et al. HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a as a result of the t(5;14)(q35;q32). Blood 2006; 108: 4198–4201.

    Article  CAS  Google Scholar 

  5. Nagel S, Scherr M, Kel A, Hornischer K, Crawford GE, Kaufmann M et al. Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-cell acute lymphoblastic leukemia by remote 3′-BCL11B enhancers and coregulation by PU.1 and HMGA1. Cancer Res 2007; 67: 1461–1471.

    Article  CAS  Google Scholar 

  6. Matakatsu H, Blair SS . The DHHC palmitoyltransferase approximated regulates Fat signaling and Dachs localization and activity. Curr Biol 2008; 18: 1390–1395.

    Article  CAS  Google Scholar 

  7. Fukata Y, Fukata M . Protein palmitoylation in neuronal development and synaptic plasticity. Nat Rev Neurosci 2010; 11: 161–175.

    Article  CAS  Google Scholar 

  8. Ohno Y, Kihara A, Sano T, Igarashi Y . Intracellular localization and tissue-specific distribution of human and yeast DHHC cysteine-rich domain-containing proteins. Biochim Biophys Acta 2006; 1761: 474–483.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the University of Maryland Cytogenetics Laboratory for its high-quality karyotype analysis that led to the identification of the subtle translocation. This work was supported by intramural funds from the Department of Pathology, University of Maryland.

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Authors and Affiliations

  1. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

    L Yu, J C Reader, C Chen, X F Zhao & Y Ning

  2. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

    J S Ha & C Lee

  3. Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA

    T York

  4. Department of Medicine and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA

    I Gojo & M R Baer

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  1. L Yu
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Correspondence to Y Ning.

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Yu, L., Reader, J., Chen, C. et al. Activation of a novel palmitoyltransferase ZDHHC14 in acute biphenotypic leukemia and subsets of acute myeloid leukemia. Leukemia 25, 367–371 (2011). https://doi.org/10.1038/leu.2010.271

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