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Pediatric early T-cell precursor leukemia with NF1 deletion and high-sensitivity in vitro to tipifarnib

Leukemia volume 24, pages 1230–1233 (2010)Cite this article

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Early T-cell precursor-acute lymphoblastic leukemia (ETP-ALL) is a newly identified high-risk pediatric subtype of ALL, originating from ETPs1 that retain multilineage differentiation potential.2 ETP-ALL is characterized by a worse response to standard intensive chemotherapy; therefore, new treatment strategies are needed to improve their outcome.1 NF1 gene, located at 17q11.2, is a negative regulator of RAS signaling pathway mutated in neurofibromatosis type 1 (Nf1), whose inactivation has been recently identified as a new proliferative hit in pediatric T-cell lymphoblastic leukemia (T-ALL).3 Tipifarnib is a farnesyltransferase inhibitor that has demonstrated in vitro and in vivo activity against many hematologic disorders as acute myeloid leukemia.4, 5 Tipifarnib acts on important signaling molecules including RAS, and promising results were obtained on in vitro sensitivity of pediatric T-ALL blast cells to tipifarnib.6

We performed high-resolution genomic screening of bone marrow samples from this patient and nine other pediatric T-ALL patients using 250K single-nucleotide polymorphism array. Parents of all the patients involved in the study signed a specific informed consent in accordance with the Declaration of Helsinki, approved by the Ethical Review Board of Policlinico S. Orsola-Malpighi, stating their consent for scientific use of results.

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Acknowledgements

We thank the Association ‘Morgan di Gianvittorio’ for funding and Ageop for support.

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Author notes

  1. C Biagi and A Astolfi: These authors contributed equally to this work.

Authors and Affiliations

  1. Pediatric Hematology and Oncology Unit ‘Lalla Seràgnoli’, University of Bologna, Bologna, Italy

    C Biagi, R Masetti, S Serravalle, M Franzoni, F Melchionda & A Pession

  2. Interdepartmental Centre for Cancer Research ‘G. Prodi’, University of Bologna, Bologna, Italy

    A Astolfi

  3. Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy

    F Chiarini

Authors
  1. C Biagi
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  2. A Astolfi
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  3. R Masetti
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  4. S Serravalle
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  5. M Franzoni
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  6. F Chiarini
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  7. F Melchionda
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  8. A Pession
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Correspondence to C Biagi.

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The authors declare no conflict of interest.

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Biagi, C., Astolfi, A., Masetti, R. et al. Pediatric early T-cell precursor leukemia with NF1 deletion and high-sensitivity in vitro to tipifarnib. Leukemia 24, 1230–1233 (2010). https://doi.org/10.1038/leu.2010.81

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