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Acute lymphoblastic leukemia associated with RCSD1–ABL1 novel fusion gene has a distinct gene expression profile from BCR–ABL1 fusion

Leukemia volume 27, pages 1422–1424 (2013)Cite this article

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De Braekeleer et al.1 published the first case of acute lymphoblastic leukemia (ALL) associated with a t(1;9)(q24;q34) and showed colocalization of bacterial artificial chromosome (BAC) clones containing the RCSD1 and ABL1 genes, suggesting the presence of a yet undescribed fusion gene. Mustjoki et al.2 identified a second patient. Sequencing of the PCR products showed that the first three exons of RCSD1 were fused to ABL1, starting at exon 4.

We obtained biological samples from patients diagnosed in Finland, United Kingdom, Kuwait and Ecuador. Five patients (three males and two females) were then included in this study (Table 1). Their age ranged from 11 to 40 years. All had B-cell ALL. Immunophenotyping showed the blasts to be CD10+, CD19+, CD22+, CD24+ and CD79a+. One patient, Pt 4, was lost to follow-up soon after diagnosis. A complete remission was achieved in three patients (Pts 1, 2 and 3) while one patient, Pt 5, was not compliant to treatment and did not achieve complete remission. Three of the four patients for whom data were available (Pts 1, 3 and 5) were still alive, survival ranging from 12 to 97 months. One patient, Pt 1, received bone marrow transplantation 31 months following diagnosis (after a first relapse) and was alive 66 months later. Another patient, Pt 3, had allogeneic hematopoietic stem cell transplantation 4 months following diagnosis but relapsed 12 months later. A third patient, Pt 2, had three bone marrow transplantations, each time following relapse, but died 84 months following diagnosis.

Table 1 Clinical and hematological characteristics of five patients with t(1;9)(q24;q34)
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References

  1. De Braekeleer E, Douet-Guilbert N, Le Bris MJ, Berthou C, Morel F, De Braekeleer M . A new partner gene fused to abl1 in a t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia. Leukemia 2007; 21: 2220–2221.

    Article  CAS  PubMed  Google Scholar 

  2. Mustjoki S, Hernesniemi S, Rauhala A, Kahkonen M, Almqvist A, Lundan T et al. A novel dasatinib-sensitive RCSD1-ABL1 fusion transcript in chemotherapy-refractory adult pre-B lymphoblastic leukemia with t(1;9)(q24;q34). Haematologica 2009; 94: 1469–1471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Inokuchi K, Wakita S, Hirakawa T, Tamai H, Yokose N, Yamaguchi H et al. RCSD1-ABL1-positive B lymphoblastic leukemia is sensitive to dexamethasone and tyrosine kinase inhibitors and rapidly evolves clonally by chromosomal translocations. Int J Hematol 2011; 94: 255–260.

    Article  CAS  PubMed  Google Scholar 

  4. Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell 2012; 22: 153–166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. De Braekeleer E, Douet-Guilbert N, Rowe D, Bown N, Morel F, Berthou C et al. ABL1 fusion genes in hematological malignancies: a review. Eur J Haematol 2011; 86: 361–371.

    Article  CAS  PubMed  Google Scholar 

  6. Roumiantsev S, de Aos IE, Varticovski L, Ilaria RL, Van Etten RA . The src homology 2 domain of Bcr/Abl is required for efficient induction of chronic myeloid leukemia-like disease in mice but not for lymphoid leukemogenesis or activation of phosphatidylinositol 3-kinase. Blood 2001; 97: 4–13.

    Article  CAS  PubMed  Google Scholar 

  7. Eyers CE, McNeill H, Knebel A, Morrice N, Arthur SJC, Cuenda A et al. The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ. Biochem J 2005; 389: 127–135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary ML . A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell 2010; 17: 198–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mak AB, Nixon AM, Moffat J . The mixed lineage leukemia (MLL) fusion-associated gene AF4 promotes CD133 transcription. Cancer Res 2012; 72: 1929–1934.

    Article  CAS  PubMed  Google Scholar 

  10. Wagner K, Mincheva A, Korn B, Lichter P, Popperl H . Pbx4, a new Pbx family member on mouse chromosome 8, is expressed during spermatogenesis. Mech Dev 2001; 103: 127–131.

    Article  CAS  PubMed  Google Scholar 

  11. Laurent A, Bihan R, Omilli F, Deschamps S, Pellerin I . PBX proteins: much more than Hox cofactors. Int J Dev Biol 2008; 52: 9–20.

    Article  CAS  PubMed  Google Scholar 

  12. Cory S, Adams JM . The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2: 647–656.

    Article  CAS  PubMed  Google Scholar 

  13. Wilson BE, Mochon E, Boxer LM . Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. Mol Cell Biol 1996; 16: 5546–5556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nomura N, Zu YL, Maekawa T, Tabata S, Akiyama T, Ishii S . Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. J Biol Chem 1993; 268: 4259–4266.

    CAS  PubMed  Google Scholar 

  15. Oltvai ZN, Milliman CL, Korsmeyer SJ . Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609–619.

    Article  CAS  PubMed  Google Scholar 

  16. Roumiantsev S, Krause DS, Neumann CA, Dimitri CA, Asiedu F, Cross NC et al. Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations. Cancer Cell 2004; 5: 287–298.

    Article  CAS  PubMed  Google Scholar 

  17. Zamecnikova A . Chromosomal translocation t(1;9)(q24;q34) in acute lymphoblastic leukemia patient involving the ABL1 gene. Leuk Res 2011; 35: e149–e150.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work has been funded in part by the ‘Ligue contre le Cancer-Comité du Finistère’.

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Authors and Affiliations

  1. Laboratoire d’Histologie, Embryologie et Cytogénétique, Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale, Brest, France

    E De Braekeleer, N Douet-Guilbert & M De Braekeleer

  2. Institut National de la Santé et de la Recherche Médicale (INSERM) U1078, Brest, France

    E De Braekeleer, N Douet-Guilbert & M De Braekeleer

  3. Service de Cytogénétique, Cytologie et Biologie de la Reproduction, Hôpital Morvan, CHRU Brest, Brest, France,

    N Douet-Guilbert & M De Braekeleer

  4. Service des Maladies du Sang, CHU Angers, Angers, France

    P Guardiola

  5. Institut National de la Santé et de la Recherche Médicale (INSERM) U892, Angers, France

    P Guardiola

  6. Northern Genetics Service, Newcastle upon Tyne, UK

    D Rowe & N Bown

  7. Department of Medicine, Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

    S Mustjoki & K Porkka

  8. Department of Hematology, Kuwait Cancer Control Center, Kuwait City, Kuwait

    A Zamecnikova & S Al Bahar

  9. Instituto de Investigaciones Biomédicas, Universidad de las Américas, Quito, Ecuador

    G Jaramillo

  10. Service d’Hématologie Clinique, Institut de Cancérologie et d’Hématologie, Hôpital Morvan, CHRU Brest, Brest, France,

    C Berthou

  11. Instituto del Cancer SOLCA, Cuenca, Ecuador

    C Ochoa

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  1. E De Braekeleer
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  2. N Douet-Guilbert
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Correspondence to E De Braekeleer or M De Braekeleer.

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De Braekeleer, E., Douet-Guilbert, N., Guardiola, P. et al. Acute lymphoblastic leukemia associated with RCSD1–ABL1 novel fusion gene has a distinct gene expression profile from BCR–ABL1 fusion. Leukemia 27, 1422–1424 (2013). https://doi.org/10.1038/leu.2012.332

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