BCR/ABL1 fluorescence in situ hybridization fusion signals on both copies of chromosome 22 in a Philadelphia-masked chronic myeloid leukemia case: implication for the therapy

  • Silvia Soriani | silvia.soriani@ospedaleniguarda.it Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy. https://orcid.org/0000-0001-7822-6550
  • Valentina Guido Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy.
  • Giambattista Bertani Department of Hematology, Niguarda Hospital, Milan, Italy.
  • Clara Cesana Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy.
  • Valentina Motta Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy.
  • Gabriella De Canal Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy.
  • Elena De Paoli Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy.
  • Silvio Veronese Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy.
  • Emanuela Bonoldi Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy.
  • Lorenza Romitti Department of Laboratory Medicine, Niguarda Hospital, Milan, Italy. https://orcid.org/0000-0002-3272-4930

Abstract

The cytogenetic hallmark of Chronic Myeloid Leukemia (CML) is the presence of Philadelphia (Ph) chromosome, which results from a reciprocal translocation t(9;22)(q34;q11). In this report, we describe a CML patient with no evidence of Ph chromosome but trisomy of chromosome 8 as single cytogenetic abnormality and a typical e14a2 (b3a2) BCR-ABL1 fusion transcript. Fluorescence In Situ Hybridization (FISH) analysis revealed an uncommon signal pattern: the fusion signals were located on both copies of chromosome 22. During the course of the disease the appearance of the p.(Tyr315Ile) mutation was recorded. To the best of our knowledge this is the first Ph chromosome-negative CML case with e14a2 (b3a2) BCR-ABL1 transcript and p.(Tyr315Ile) mutation.

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References

Swerdlow SH, Campo E, Lee Harris N, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 2017; Revised 4th Edition. pp 30-36.

Heim S, Mitelman F. Cancer Cytogenetics. 3 rd ed. Wiley-Blackwell (John Wiley & Sons Ltd); 2015. pp 179-196. DOI: https://doi.org/10.1002/9781118795569

Martín-Subero JI, Lahortiga I, Gómez E,et al. Insertion (22;9)(q11;q34q21) in a patient with chronic myeloid leukemia characterized by fluorescence in situ hybridization. Cancer Genet Cytogenet. 2001;125:167-70. DOI: https://doi.org/10.1016/S0165-4608(00)00370-8

The Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer. https://mitelmandatabase.isb-cgc.org

Vieira L, Alves AC, Marques B, et al. Insertion of the 5' part of BCR within the ABL gene at 9q34 in a Philadelphia-negative chronic myeloid leukemia. Cancer Genet Cytogenet. 1999;114:17-21. DOI: https://doi.org/10.1016/S0165-4608(99)00036-9

Seong D, Kantarjian HM, Albitar M, et al. Analysis of Philadelphia chromosome-negative BCR-ABL-positive chronic myelogenous leukemia by hypermetaphase fluorescence in situ hybridization. Ann Oncol. 1999 Aug;10:955-9. DOI: https://doi.org/10.1023/A:1008349405763

Costa D, Espinet B, Queralt R, et al. Chimeric BCR/ABL gene detected by fluorescence in situ hybridization in three new cases of Philadelphia chromosome-negative chronic myelocytic leukemia. 2003;141:114-9. DOI: https://doi.org/10.1016/S0165-4608(02)00662-3

Stam K, Heisterkamp N, Reynolds FH Jr, Groffen J. Evidence that the phl gene encodes a 160,000-dalton phosphoprotein with associated kinase activity. Mol Cell Biol. 1987;7:1955-60. DOI: https://doi.org/10.1128/MCB.7.5.1955

Neviani P. Genetic events other than BCR-ABL1. Curr Hematol Malig Rep. 2014;9:24-32. DOI: https://doi.org/10.1007/s11899-013-0194-x

Faderl S, Talpaz M, Estrov Z, et al. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341:164-72. DOI: https://doi.org/10.1056/NEJM199907153410306

Skorski T. Genetic mechanisms of chronic myeloid leukemia blastic transformation. Curr Hematol Malig Rep. 2012;7:87-93. DOI: https://doi.org/10.1007/s11899-012-0114-5

Morris CM, Reeve AE, Fitzgerald PH, et al. Genomic diversity correlates with clinical variation in Ph-negative chronic myeloid leukaemia. Nature. 1986;320:281-3. DOI: https://doi.org/10.1038/320281a0

Inazawa J, Nishigaki H, Takahira H, et al. Rejoining between 9q+ and Philadelphia chromosomes results in normal-looking chromosomes 9 and 22 in Ph1-negative chronic myelocytic leukemia. Hum Genet. 1989;83:115-8. DOI: https://doi.org/10.1007/BF00286701

De Melo VA, Milojkovic D, Marin D, et al. Deletions adjacent to BCR and ABL1 breakpoints occur in a substantial minority of chronic myeloid leukemia patients with masked Philadelphia rearrangements. Cancer Genet Cytogenet. 2008;15;182:111-5. DOI: https://doi.org/10.1016/j.cancergencyto.2008.01.007

Luatti S, Baldazzi C, Marzocchi G, et al. Cryptic BCR-ABL fusion gene as variant rearrangement in chronic myeloid leukemia: molecular cytogenetic characterization and influence on TKIs therapy. Oncotarget. 2017;8:29906-29913. DOI: https://doi.org/10.18632/oncotarget.15369

Virgili A, Brazma D, Reid AG, et al. FISH mapping of Philadelphia negative BCR/ABL1 positive CML. Mol Cytogenet. 2008;18;1-14. DOI: https://doi.org/10.1186/1755-8166-1-14

Ercaliskan A, and Eskazan A.E. The impact of BCR-ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia. Cancer. 2018;124:3806-3818. DOI: https://doi.org/10.1002/cncr.31408

Published
2021-03-24
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Case Reports
Keywords:
Chronic Myeloid Leukemia, CML, Philadelphia chromosome-negative, masked Philadelphia, p.(Tyr315Ile) mutation
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How to Cite
Soriani, S., Guido, V., Bertani, G., Cesana, C., Motta, V., De Canal, G., De Paoli, E., Veronese, S., Bonoldi, E., & Romitti, L. (2021). BCR/ABL1 fluorescence <em>in situ</em&gt; hybridization fusion signals on both copies of chromosome 22 in a Philadelphia-masked chronic myeloid leukemia case: implication for the therapy. Hematology Reports, 13(1). https://doi.org/10.4081/hr.2021.8795