Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Detection of PICALM-MLLT10 (CALM-AF10) and outcome in children with T-lineage acute lymphoblastic leukemia

Leukemia volume 27, pages 2419–2421 (2013)Cite this article

Subjects

Approximately 10–15% of pediatric patients with acute lymphoblastic leukemia (ALL) have a T-cell phenotype. The prognosis of these patients has improved over the last years, owing to the use of more intensive treatment strategies.1 Characterization of molecular alterations with prognostic impact in T-ALL may be of great help for an early identification of patients at high risk (HR) of failure in whom more intensive treatments, including allogeneic hematopoietic stem cell transplantation, may be considered.

PICALM (clathrin-assembly protein-like lymphoid myeloid leukemia gene)-MLLT10 (formerly CALM-AF10) results from a recurring t(10;11)(p13;q14-21) chromosomal translocation and is the most frequent fusion transcript detected in patients with T-ALL, at an overall rate of 10%, including both adults and children.2 This translocation fuses PICALM (or CALM) and MLLT10 (also called AF10). The Groupe Français de Cytogénétique Hématologique firstly observed this translocation in a patient with histiocytic lymphoma.3 The immunophenotypic characterization of the leukemic cell bearing this fusion gene showed that mature PICALM-MLLT10-positive cases expressed CD5, T-cell receptor (TCR) γ/δ and CD4 or CD8 (or both), whereas immature cases, which are currently defined as early-T, expressed few T-lineage markers other than CD5, TdT, cCD3 and CD7, and were often positive for CD13, CD33 or CD34.4 The presence of PICALM-MLLT10 has been associated with a poor prognosis and several studies included very few children with T-ALL.4, 5, 6, 7

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Pui C-H, Evans WE . Treatment of acute lymphoblastic leukemia. New Engl J Med 2006; 354: 166–178.

    Article  CAS  Google Scholar 

  2. Graux C, Cools J, Michaux L, Vandenberghe P, Haghemeijer A . Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia 2006; 20: 1496–1510.

    Article  CAS  Google Scholar 

  3. Groupe Français de Cytogénétique Hématologique (GFCH). t(10;11)(p13-14;q14-21): a new recurrent translocation in T-cell acute lymphoblastic leukemia. Gene Chromosomes Cancer 1991; 3: 411–415.

    Article  Google Scholar 

  4. Asnafi V, Radford-Weiss I, Dastugue N, Bayle C, Leboeuf D, Charrin C et al. CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRγδ lineage. Blood 2003; 102: 1000–1006.

    Article  CAS  Google Scholar 

  5. Caudell D, Aplan PD . The role of CALM-AF10 gene fusion in acute leukemia. Leukemia 2008; 22: 678–685.

    Article  CAS  Google Scholar 

  6. van Grotel M, Meijerink JPP, Beverloo HB, Langerak AW, Buijs-Gaddines JG, Schneider P et al. The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols. Haematologica 2006; 91: 1212–1221.

    Google Scholar 

  7. Narita M, Shimizu K, Hayashi Y, Taki T, Taniwaki M, Hosoda F et al. Consistent detection of CALM-AF10 chimaeric transcript in haematological malignancies with t(10;11)(p13;q14) and identification of novel transcripts. Br J Haematol 1999; 105: 928–937.

    Article  CAS  Google Scholar 

  8. Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grümayer R, Möricke A et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood 2011; 118: 2077–2084.

    Article  CAS  Google Scholar 

  9. Ballerini P, Landman-Parker J, Cayuela JM, Asnafi V, Labopin M, Gandemer V et al. Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome. Haematologica 2008; 93: 1658–1665.

    Article  Google Scholar 

  10. Van Vlierberghe P, Pieters R, Beverloo HB, Meijerink JPP . Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukemia. Br J Hematol 2008; 143: 153–168.

    Article  CAS  Google Scholar 

  11. Okada Y, Jiang Q, Lemieux M, Jeannotte L, Su L, Zhang Y . Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L. Nat Cell Biol 2006; 8: 1017–1024.

    Article  CAS  Google Scholar 

  12. Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation trough genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia 2013; 27: 813–822.

    Article  CAS  Google Scholar 

  13. Mulaw MA, Krause AJ, Deshpande AJ, Krause LF, Rouhi A, La Starza R et al. CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12. Leukemia 2012; 26: 1012–1019.

    Article  CAS  Google Scholar 

  14. Grossman V, Bacher U, Kohlmann A, Artusi V, Klein HU, Dugas M et al. EZH2 mutations and their association with PICALM-MLLT10 positive acute leukaemia. Br J Haematol 2012; 157: 387–390.

    Article  Google Scholar 

  15. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 2012; 492: 108–112.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from Fondazione Città della Speranza (Padova); Fondazione Tettamanti (Monza). LLN was partially supported by an AIRC (Italian Association of Cancer Research) grant (MFAG 2009–2011). We gratefully thank all medical doctors of the AIEOP centers who treated children and collected diagnostic samples.

Author contributions

LLN designed the study, supervised the research, collected the data and wrote the manuscript; EM, MT and CC performed the molecular analyses; GB and BB performed the immunophenotyping characterization; DS and MGV collected the trials data and performed the statistical analyses; GC, GB and AB were responsible for collecting the samples and performing the diagnostic analyses and MRD; GM and VC were responsible for AIEOP ALL-2000 and ALL-R-2006 studies; EB, FC, ML, CMe, CMi., AP, RP and NS provided the data and samples; CR, FL, MA, MGV and VC collaborated in writing the manuscript.

Author information

Authors and Affiliations

  1. Center of Pediatric Hematology Oncology, Catania, Italy

    L Lo Nigro, E Mirabile, M Tumino & C Caserta

  2. University of Milano-Bicocca, Ospedale Nuovo San Gerardo, Monza, Italy

    G Cazzaniga, C Rizzari, G Masera, A Biondi & V Conter

  3. University of Milano-Bicocca, Milano, Italy

    D Silvestri & M Valsecchi

  4. Dipartimento di Salute della Donna e del Bambino, Padova, Italy

    B Buldini, C Messina & G Basso

  5. Ospedale Regina Margherita, Torino, Italy

    E Barisone

  6. Sezione di Oncologia Pediatrica Seconda Università di Napoli, Naples, Italy,

    F Casale

  7. Roma, IRCCS Ospedale Pediatrico Bambino Gesù, Pavia, Italy,

    M Luciani & F Locatelli

  8. Università di Pavia, Pavia, Italy

    F Locatelli

  9. Genova Gaslini, Istituto G Gaslini, Genova, Italy,

    C Micalizzi

  10. Ospedale S. Orsola, Bologna, Italy

    A Pession

  11. Dipartimento di Emato-Oncologia, AORN Santobono-Pausilipon, Napoli, Italy

    R Parasole

  12. Policlinico, Bari, Italy

    N Santoro

  13. Azienda Ospedaliera Universitaria Meyer Children Hospital, Firenze, Italy

    M Aricò

Authors
  1. L Lo Nigro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Mirabile
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Tumino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Caserta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G Cazzaniga
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Rizzari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D Silvestri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B Buldini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Barisone
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F Casale
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Luciani
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. F Locatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. C Messina
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. C Micalizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. A Pession
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. R Parasole
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. N Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. G Masera
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. G Basso
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. M Aricò
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. M Valsecchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. A Biondi
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. V Conter
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of AIEOP—Scientific Committee of ALL

Corresponding author

Correspondence to L Lo Nigro.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lo Nigro, L., Mirabile, E., Tumino, M. et al. Detection of PICALM-MLLT10 (CALM-AF10) and outcome in children with T-lineage acute lymphoblastic leukemia. Leukemia 27, 2419–2421 (2013). https://doi.org/10.1038/leu.2013.149

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2013.149

This article is cited by

Search

Advanced search

Quick links