Activation of a novel palmitoyltransferase ZDHHC14 in acute biphenotypic leukemia and subsets of acute myeloid leukemia (original) (raw)

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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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

Authors

  1. L Yu
  2. J C Reader
  3. C Chen
  4. X F Zhao
  5. J S Ha
  6. C Lee
  7. T York
  8. I Gojo
  9. M R Baer
  10. Y Ning

Corresponding author

Correspondence toY Ning.

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The authors declare no conflict of interest.

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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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