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Identification of E6A2 BCR-ABL fusion in a Philadelphia-positive CML

Leukemia volume 14, pages 2011–2012 (2000)Cite this article

Molecular analysis of the Philadelphia (Ph) chromosome has shown that the 3′ sequences of the tyrosine kinase c-ABL proto-oncogene (located on chromosome 9q34) and the 5′ sequences of the BCR gene (located on chromosome 22q11) are joined in the Ph translocation. The various breakpoints on the two chromosomes give different fusion transcripts with different BCR-ABL junctions. Most chronic myeloid leukemia (CML) patients with Ph chromosome express the BCR-ABL transcript with the most frequent junctions b3a2 (e14a2) or b2a2 (e13a2) corresponding to the BCR gene breakpoints located in a central region called the ‘major breakpoint cluster region’ (M-bcr). On the other hand, a shortened BCR-ABL transcript with an e1a2 type of junction (m-bcr or ‘minor breakpoint cluster region’ on the BCR gene) is frequently expressed in patients with Ph-positive acute lymphoid leukemia (ALL). Only sporadic cases express the other junctions; e19a2, b2a3 or b3a3.12 We have studied the case of a CML patient with a Ph chromosome expressing the rare e6a2 junction of the BCR-ABL fusion gene.

This patient, a 50-year-old man, was referred to our center in 1999 with a high white blood cell (WBC) count. He had in 1990, a medical history of idiopathic thrombocytopenic purpura (ITP), which required a splenectomy to be cured. The first blood count showed 63.6×109/1 WBC with 1% blast cells, 227 × 109/1 platelets and 12.4 g/dl hemoglobin. The bone marrow was hypercellular with a granulocytic predominance. The patient was treated according to arm A of a randomized trial of the French Bone Marrow Transplantation Society, which compared initial unpurged autologous peripheral blood stem cell transplantation followed by interferon-α plus cytarabine (arm A) to standard treatment with interferon-α plus cytarabine (arm B).

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References

  1. Melo JV . The molecular biology of chronic myeloid leukemia Leukemia 1996 10: 751–756

    CAS  PubMed  Google Scholar 

  2. Saglio G, Guerrasio A, Rosso C, Tassinari A, Serra A, Rege-Cambrin G, Mazza U, Gavosto F . New type of BCR/ABL junction in Philadelphia chromosome-positive chronic myelogenous leukemia Blood 1990 76: 1819–1824

    CAS  PubMed  Google Scholar 

  3. Chiesa J, Bureau JP . In situ Hybridization on chromosomes: clinical applications. In: Morel G (ed) Visualisation of Nucleic Acids CRC Press: Boca Raton, FL 1995 pp 185–199

    Google Scholar 

  4. Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction Anal Biochem 1987 162: 156–159

    Article  CAS  Google Scholar 

  5. Melo JV, Kent NS, Yan XH, Goldman JM . Controls for reverse transcriptase-polymerase chain reaction amplification of BCR-ABL transcripts Blood 1994 84: 3984–3986

    CAS  PubMed  Google Scholar 

  6. Van Dongen JJM, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Gonzalez Diaz M, Malec M, Langerak AW, San Miguel JF, Biondi A . Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease Leukemia 1999 13: 1901–1928

    Article  CAS  Google Scholar 

  7. Rey JM, Pujol P, Callier P, Cavailles V, Freiss G, Maudelonde T, Brouillet JP . Semiquantitative reverse transcription-polymerase chain reaction to evaluate the expression patterns of genes involved in the oestrogen pathway J Mol Endocrinol 2000 24: 433–440

    Article  CAS  Google Scholar 

  8. Cross NCP, Melo JV, Feng L, Goldman JM . An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL fusion mRNAs in haematoligical disorders Leukemia 1994 8: 186–189

    CAS  PubMed  Google Scholar 

  9. Hochhaus A, Reiter A, Skladny H, Melo JV, Sick C, Berger U, Guo JQ, Arhlingaus RB, Hehlmann R, Goldman JM, Cross NCP . A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome-negative chronic myelogenous leukemia Blood 1996 88: 2236–2240

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was support by the Regional Hospital Center of Montpellier. We thank Dr Jean Marc Rey for sequencing, Mireille Audema and Line Lioure for technical assistance, Dr Isabelle Touitou for sientific advice and Andrew Goldsborough for manuscript comments.

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  1. Génétique Moléculaire et Chromosomique, Hôpital A de Villeneuve, Montpellier, France

    M Dupont

  2. Service de Médecine Intern B, Faculté de Médecine, Hôpital Caremeau, Nîmes, France

    E Jourdan

  3. Laboratoire de Cytogénétique, Faculté de Médecine, Hôpital Caremeau, Nîmes, France

    J Chiesa

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Dupont, M., Jourdan, E. & Chiesa, J. Identification of E6A2 BCR-ABL fusion in a Philadelphia-positive CML. Leukemia 14, 2011–2012 (2000). https://doi.org/10.1038/sj.leu.2401916

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