1. bookVolume 23 (2015): Issue 2 (June 2015)
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
access type Open Access

Co-expression of the CBFβ-MYH11 and BCR-ABL fusion genes in chronic myeloid leukaemia / Coexistenţa genelor de fuziune CBFβ-MYH11 şi BCR-ABL în leucemia mieloidă cronică

Published Online: 23 Jun 2015
Volume & Issue: Volume 23 (2015) - Issue 2 (June 2015)
Page range: 221 - 230
Received: 12 Nov 2014
Accepted: 13 Apr 2015
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

The coexistence of t(9;22) and inv(16) has been described in a very limited number of cases of CML, de novo or therapy-related AML. We report a patient with CML who presented both inversion of chromosome 16 and Philadelphia chromosome and evolved towards the blast phase under treatment with Imatinib. Laboratory diagnosis and monitoring was made by flow cytometry, conventional cytogenetics and molecular genetics techniques. The inv(16), detected by karyotyping in the Philadelphia chromosome positive clone at the moment of the blast transformation, was retrospectively assessed by means of real-time PCR, and was proved to have been present since diagnosis. The bone marrow biopsy performed in the blast phase of CML confirmed the presence of blasts belonging to the myeloid lineage, with indications of monocytic differentiation, frequently associated with inv(16). Moreover, the case also associated a F359V tyrosine kinase domain mutation, resulting in intermediate resistance to Imatinib and Nilotinib, which imposed therapy-switch to Dasatinib. In our case the evolution was progressive, followed by death due to lack of response to tyrosine kinase inhibitors, 18 months after diagnosis. The coexistence of t(9;22) and inv(16) in CML seems to be associated with an aggressive clinical evolution and resistance to tyrosine kinase inhibitor therapy. Due to the very small number of cases described in literature, therapeutic decisions are still difficult for patients displaying these abnormalities

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Cuvinte cheie

1. Liu P, Tarle SA, Hajra A, Claxton DF, Marlton P, Freedman M, et al. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science. 1993;261(5124):1041-4. DOI: 10.1126/science.835151810.1126/science.8351518Search in Google Scholar

2. Kundu M, Liu PP. Function of the inv(16) fusion gene CBFB-MYH11. Curr Opin Hematol. 2001;8(4):201-5. DOI: 10.1097/00062752-200107000-0000410.1097/00062752-200107000-00004Search in Google Scholar

3. Calabretta B, Perrotti D. The biology of CML blast crisis. Blood. 2004;103(11):4010-22. DOI: 10.1182/ blood-2003-12-411110.1182/blood-2003-12-4111Search in Google Scholar

4. Colovic M, Jankovic G, Bila J, Djordjevic V, Wiernik PH. Inversion of chromosome 16 in accelerated phase of chronic myeloid leukaemia: report of a case and review of the literature. Med Oncol. 1998;15(3):199-201. DOI: 10.1007/BF0282193910.1007/BF02821939Search in Google Scholar

5. Enright H, Weisdorf D, Peterson L, Rydell RE, Kaplan ME, Arthur DC. Inversion of chromosome 16 and dysplastic eosinophils in accelerated phase of chronic myeloid leukemia. Leukemia. 1992;6(5):381-4.Search in Google Scholar

6. Myint H, Ross FM, Hall JL, Hamblin TJ. Early transformation to acute myeloblastic leukaemia with the acquisition of inv(16) in Ph positive chronic granulocytic leukaemia. Leuk Res. 1997;21(5):473-4. DOI: 10.1016/ S0145-2126(97)00070-210.1016/S0145-2126(97)00070-2Search in Google Scholar

7. Heim S, Christensen BE, Fioretos T, Sorensen AG, Pedersen NT. Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia. Cancer Genet Cytogenet. 1992;59(1):35-8. DOI: 10.1016/0165-4608(92)90154-Z10.1016/0165-4608(92)90154-ZSearch in Google Scholar

8. Miura I, Takatsu H, Yamaguchi A, Hashimoto K, Nimura T, Nishinari T, et al. Standard Ph chromosome, t(9;22)(q34;q11), as an additional change in a patient with acute myelomonocytic leukemia (M4Eo) associated with inv(16)(p13q22). Am J Hematol. 1994;45(1):94-6. DOI: 10.1002/ajh.283045011810.1002/ajh.28304501188250017Search in Google Scholar

9. Patel BB, Mohamed AN, Schiffer CA. „Acute myelogenous leukemia like” translocations in CML blast crisis: two new cases of inv(16)/t(16;16) and a review of the literature. Leuk Res. 2006;30(2):225-32. DOI: 10.1016/j.leukres.2005.06.00810.1016/j.leukres.2005.06.00816076492Search in Google Scholar

10. Wu Y, Slovak ML, Snyder DS, Arber DA. Coexistence of inversion 16 and the Philadelphia chromosome in acute and chronic myeloid leukemias : report of six cases and review of literature. Am J Clin Pathol. 2006;125(2):260-6. DOI: 10.1309/F0MX-5CL8- CEDY-3W86 DOI: 10.1309/F0MX5CL8CEDY3W86Search in Google Scholar

11. Tirado CA, Valdez F, Klesse L, Karandikar NJ, Uddin N, Arbini A, et al. Acute myeloid leukemia with inv(16) with CBFB-MYH11, 3’CBFB deletion, variant t(9;22) with BCR-ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review. Cancer Genet Cytogenet. 2010;200(1):54-9. DOI: 10.1016/j.cancergencyto. 2010.03.001Search in Google Scholar

12. Gabert J, Beillard E, van der Velden VH, Bi W, Grimwade D, Pallisgaard N, et al. Standardization and quality control studies of ‚real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program. Leukemia. 2003;17(12):2318-57. DOI: 10.1038/sj.leu.240313510.1038/sj.leu.240313514562125Search in Google Scholar

13. Gribble SM, Reid AG, Roberts I, Grace C, Green AR, Nacheva EP. Genomic imbalances in CML blast crisis: 8q24.12-q24.13 segment identified as a common region of over-representation. Genes Chromosomes Cancer. 2003;37(4):346-58. DOI: 10.1002/gcc.1017310.1002/gcc.1017312800146Search in Google Scholar

14. Han E, Lee H, Kim M, Kim Y, Han K, Lee SE, et al. Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities. Blood Res. 2014;49(1):22-8. DOI: 10.5045/ br.2014.49.1.2210.5045/br.2014.49.1.22397495224724063Search in Google Scholar

15. Merzianu M, Medeiros LJ, Cortes J, Yin C, Lin P, Jones D, et al. inv(16)(p13q22) in chronic myelogenous leukemia in blast phase: a clinicopathologic, cytogenetic, and molecular study of five cases. Am J Clin Pathol. 2005;124(5):807-14. DOI: 10.1309/3HFE16DKMB1DBFMN10.1309/3HFE16DKMB1DBFMNSearch in Google Scholar

16. Dai HP, Xue YQ, Wu LL, Pan JL, Gong YL, Wu YF, et al. p210 BCR/ABL1 as a secondary change in a patient with acute myelomonocytic leukemia (M4Eo) with inv(16). Int J Hematol. 2012;96(6):814-7. DOI: 10.1007/s12185-012-1190-y10.1007/s12185-012-1190-y23054652Search in Google Scholar

17. Bustamante D, Chan KR, Czuchlewski DR, Saadi AA. Patterns of BCR breakpoints in patients with coexisting inv(16)(p13.1q22) and t(9;22)(q34;q11.2). Int J Hematol. 2012;95(3):324-6. DOI: 10.1007/s12185-011-0990-910.1007/s12185-011-0990-922370710Search in Google Scholar

18. Ninomiya S, Kanemura N, Tsurumi H, Kasahara S, Hara T, Yamada T, et al. Coexistence of inversion 16 and the Philadelphia chromosome comprising P190 BCR/ABL in chronic myeloid leukemia blast crisis. Int J Hematol. 2011;93(6):806-10. DOI: 10.1007/s12185-011-0854-310.1007/s12185-011-0854-321523337Search in Google Scholar

19. Grardel N, Roumier C, Soenen V, Lai JL, Plantier I, Gheveart C, et al. Acute myeloblastic leukemia (AML) with inv (16)(p13;q22) and the rare I type CBFbeta- MYH11 transcript: report of two new cases. Leukemia. 2002;16(1):150-1. DOI: 10.1038/sj.leu.240233210.1038/sj.leu.240233211840275Search in Google Scholar

20. Roth CG, Contis L, Gupta S, Agha M, Safyan E. De novo acute myeloid leukemia with Philadelphia chromosome (BCR-ABL) and inversion 16 (CBFB- MYH11): report of two cases and review of the literature. Leuk Lymphoma. 2011;52(3):531-5. DOI: 10.3109/10428194.2010.53894110.3109/10428194.2010.53894121281226Search in Google Scholar

21. Soverini S, Hochhaus A, Nicolini FE, Gruber F, Lange T, Saglio G, et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood. 2011;118(5):1208-15. DOI: 10.1182/ blood-2010-12-326405 10.1182/blood-2010-12-32640521562040Search in Google Scholar

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