The Effect of inv(3)/t(3;3) and 7th Chromosome Abnormalities on Prognosis in Patients with Acute Myeloid Leukemia

Yıl 2024, Cilt: 11 Sayı: 3, 334 - 339, 30.09.2024

Ayşe Gül Bayrak Tokaç , Gülçin Bağatır , Simge Erdem , Kıvanç Çefle , Şükrü Öztürk , Mustafa Nuri Yenerel , Akif Selim Yavuz , Meliha Nalcaci , Şükrü Palanduz

https://doi.org/10.34087/cbusbed.1406447

Öz

Acute Myeloid Leukemia (AML) is a stem cell disease characterized by the overproduction of neoplastic clonal myeloid stem cells. The most important factors in its etiology are genetic disorders caused by chromosomal abnormalities or isolated gene mutations. According to the World Health Organization (WHO) classification, the identification of genetic abnormalities in AML plays an important role in risk stratification and determination of treatment options. WHO classification inv(3)(q21q26.2)/ t(3;3)(q21;q26.2) occurs in 1-2% of AML cases. It can also be seen in patients with de novo or post-treatment transformation from Myelodysplastic Syndrome (MDS) or blast crisis Chronic Myeloid Leukemia (CML) to AML. De novo inv(3)/t(3;3) causes an aggressive form of leukemia that does not respond to chemotherapy and has a poor prognosis, with a 5-year survival of less than 10%. The inv(3)/t(3;3) abnormality is often accompanied by monosomy 7 or del(7q). The presence of monosomy 7/del(7q) as a secondary abnormality is a finding that worsens the prognosis. It has been reported that allogeneic stem cell transplantation (Allo-SCT) is the most appropriate treatment option in patients with this abnormality due to resistance to chemotherapy.
In this study, among 734 cases with a prediagnosis/diagnosis of AML (including AML transformed from CML or MDS), cases in which inv(3)/t(3;3) and chromosome 7 abnormalities were detected together were discussed. As a result, in cases where these abnormalities are found together, Allo-SCT is the only treatment that expending life time of patients.

Anahtar Kelimeler

Acute Myeloid Leukemia, inv(3)/t(3;3), Monosomy 7, del(7q), Allogeneic Stem Sell Transplantation

Akut Miyeloid Lösemi’li Olgularda inv(3)/t(3;3) ile 7.Kromozomun Anomalilerinin Prognoza Etkisi

Öz

Akut Miyeloid Lösemi (AML), neoplastik klonal miyeloid kök hücrelerin aşırı üretimiyle karakterize bir kök hücre hastalığıdır. Etyolojisindeki en önemli etkenler kromozom anomalileri veya izole gen mutasyonları yoluyla oluşan genetik bozukluklardır. Dünya Sağlık Örgütü’nün (DSÖ) sınıflandırmasına göre, AML’de görülen genetik anomalilerin tanımlanması, hastalığın risk sınıflandırmasında ve tedavi seçeneklerinin belirlenmesinde önemli bir rol oynar. DSÖ’nün sınıflandırmasında yer alan inv(3)(q21q26.2)/t(3;3)(q21;q26.2), AML’li olguların %1-2’sinde görülür. Ayrıca, de novo yada tedavi sonrası Miyelodisplastik Sendrom’dan (MDS) ya da blast kriz Kronik Miyeloid Lösemi’den (KML) AML’ye dönüşüm gösteren olgularda da görülen bir anomalidir. De novo gelişen inv(3)/t(3;3), kemoterapiye yanıt vermeyen, prognozu kötü olan agresif bir lösemi formuna neden olur ve 5 yıllık yaşam süresi %10’dan azdır. İnv(3)/t(3;3) anomalisine sıklıkla monozomi 7 ya da del(7q) eşlik eder. Sekonder anomali olarak monozomi 7/del(7q)’nun varlığı; prognozu daha da kötüleştiren bir bulgudur. Bu anomaliye sahip olgularda kemoterapiye direnç sebebiyle en uygun tedavi seçeneğinin allojenik kemik iliği transplantasyonu (Allo-KİT) olduğu bildirilmiştir.
Bu çalışmada, 734 AML ön tanı/tanılı olgu (KML ya da MDS’den transforme AML dahil) arasından inv(3)/t(3;3) ve 7.kromozomun anomalilerinin birlikte saptandığı olgular tartışılmıştır. Sonuç olarak bu anomalilerinin birlikte saptandığı durumlarda Allo-KİT hastayı yaşama bağlayan tek tedavi seçeneği olabilir.

Anahtar Kelimeler

Akut Miyeloid Lösemi, inv(3)/t(3;3), Monozomi 7, del(7q), Allojenik kemik iliği transplantasyonu

Etik Beyan

Çalışma için İstanbul Tıp Fakültesi Klinik Araştırmalar Etik Kurulu’ndan onay alındı (Karar tarih/sayı: 17.11.2023/23).

Teşekkür

Yazarlar, Covid-19 pandemi sürecinde vefat eden Dr. Ali Ucur'a sitogenetik analizlerdeki büyük desteğinden dolayı teşekkür ederler.

Kaynakça

• 1. Pelcovits, A., & Niroula, R. (2020). Acute Myeloid Leukemia: A Review. Rhode Island medical journal (2013), 103(3), 38–40.
• 2. Arber, D. A., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M. J., Le Beau, M. M., Bloomfield, C. D., Cazzola, M., & Vardiman, J. W. (2016). The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 127(20), 2391–2405.
• 3. Arber DA, Brunning RD, Le Beau MM, et al. Acute myeloid leukaemia (AML) and related precursor neoplasms. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon, France: IARC Press, 2008:110-44.
• 4. Weisser, M., Haferlach, C., Haferlach, T., & Schnittger, S. (2007). Advanced age and high initial WBC influence the outcome of inv(3) (q21q26)/t(3;3) (q21;q26) positive AML. Leukemia & lymphoma, 48(11), 2145–2151.
• 5. Lugthart, S., Gröschel, S., Beverloo, H. B., Kayser, S., Valk, P. J., van Zelderen-Bhola, S. L., Jan Ossenkoppele, G., Vellenga, E., van den Berg-de Ruiter, E., Schanz, U., Verhoef, G., Vandenberghe, P., Ferrant, A., Köhne, C. H., Pfreundschuh, M., Horst, H. A., Koller, E., von Lilienfeld-Toal, M., Bentz, M., Ganser, A., … Döhner, H. (2010). Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 28(24), 3890–3898.
• 6. Shi, G., Weh, H. J., Dührsen, U., Zeller, W., & Hossfeld, D. K. (1997). Chromosomal abnormality inv(3)(q21q26) associated with multilineage hematopoietic progenitor cells in 5-3hematopoietic malignancies. Cancer genetics and cytogenetics, 96(1), 58–63.
• 7. Sun, J., Konoplev, S. N., Wang, X., Cui, W., Chen, S. S., Medeiros, L. J., & Lin, P. (2011). De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 24(3), 384–389.
• 8. Chan, L. C., Kwong, Y. L., Liu, H. W., Chan, T. K., Todd, D., & Ching, L. M. (1992). Cytogenetic analysis of hematologic malignancies in Hong Kong. A study of 98 cases. Cancer genetics and cytogenetics, 62(2), 154–159.
• 9. Gröschel, S., Sanders, M. A., Hoogenboezem, R., de Wit, E., Bouwman, B., Erpelinck, C., van der Velden, V., Havermans, M., Avellino, R., van Lom, K., Rombouts, E. J., van Duin, M., Döhner, K., Beverloo, H. B., Bradner, J. E., Döhner, H., Löwenberg, B., Valk, P., Bindels, E., de Laat, W., … Delwel, R. (2014). A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell, 157(2), 369–381.
• 10. Ottema, S., Mulet-Lazaro, R., Beverloo, H. B., Erpelinck, C., van Herk, S., van der Helm, R., Havermans, M., Grob, T., Valk, P., Bindels, E., Haferlach, T., Haferlach, C., Smeenk, L., & Delwel, R. (2020). Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia. Blood, 136(2), 224–234.
• 11. Hinai, A. A., & Valk, P. J. (2016). Review: Aberrant EVI1 expression in acute myeloid leukaemia. British journal of haematology, 172(6), 870–878.
• 12. Fontenay-Roupie, M., Bouscary, D., Melle, J., Viguié, F., Picard, F., Guesnu, M., & Dreyfus, F. (1997). Expression of the transcription factor Evi-1 in human erythroleukemia cell lines and in leukemias. Hematology and cell therapy, 39(1), 5–10.
• 13. Russell, M., Thompson, F., Spier, C., & Taetle, R. (1993). Expression of the EVI1 gene in chronic myelogenous leukemia in blast crisis. Leukemia, 7(10), 1654–1657.
• 14. Gröschel, S., Lugthart, S., Schlenk, R. F., Valk, P. J., Eiwen, K., Goudswaard, C., van Putten, W. J., Kayser, S., Verdonck, L. F., Lübbert, M., Ossenkoppele, G. J., Germing, U., Schmidt-Wolf, I., Schlegelberger, B., Krauter, J., Ganser, A., Döhner, H., Löwenberg, B., Döhner, K., & Delwel, R. (2010). High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 28(12), 2101–2107.
• 15. Fichelson, S., Dreyfus, F., Berger, R., Melle, J., Bastard, C., Miclea, J. M., & Gisselbrecht, S. (1992). Evi-1 expression in leukemic patients with rearrangements of the 3q25-q28 chromosomal region. Leukemia, 6(2), 93–99.
• 16. Lawrie, A., Stevenson, D. A., Doig, T. N., Vickers, M. A., & Culligan, D. J. (2012). Acute myeloid leukemia presenting in a mother and daughter pair with the identical acquired karyotypic abnormality consisting of inversion 3q21q26 and monosomy 7: a review of possible mechanisms. Cancer genetics, 205(11), 599–602.
• 17. Cordoba, I., González-Porras, J. R., Nomdedeu, B., Luño, E., de Paz, R., Such, E., Tormo, M., Vallespi, T., Collado, R., Xicoy, B., Andreu, R., Muñoz, J. A., Solé, F., Cervera, J., del Cañizo, C., & Spanish Myelodysplastic Syndrome Registry (2012). Better prognosis for patients with del(7q) than for patients with monosomy 7 in myelodysplastic syndrome. Cancer, 118(1), 127–133.
• 18. Greenberg, P. L., Tuechler, H., Schanz, J., Sanz, G., Garcia-Manero, G., Solé, F., Bennett, J. M., Bowen, D., Fenaux, P., Dreyfus, F., Kantarjian, H., Kuendgen, A., Levis, A., Malcovati, L., Cazzola, M., Cermak, J., Fonatsch, C., Le Beau, M. M., Slovak, M. L., Krieger, O., … Haase, D. (2012). Revised international prognostic scoring system for myelodysplastic syndromes. Blood, 120(12), 2454–2465.
• 19. Hartmann, L., Haferlach, C., Meggendorfer, M., Kern, W., Haferlach, T., & Stengel, A. (2019). Myeloid malignancies with isolated 7q deletion can be further characterized by their accompanying molecular mutations. Genes, chromosomes & cancer, 58(10), 698–704.
• 20. Mohanty, P., Korgaonkar, S., Shanmukhaiah, C., Ghosh, K., & Vundinti, B. R. (2016). Cytogenetic abnormalities and genomic copy number variations in EPO (7q22) and SEC-61(7p11) genes in primary myelodysplastic syndromes. Blood cells, molecules & diseases, 59, 52–57.
• 21. Tripputi, P., Cassani, B., Alfano, R., Graziani, D., Cigognini, D., Doi, P., Bignotto, M., Corneo, G., & Coggi, G. (2001). Chromosome 7 monosomy and deletions in myeloproliferative diseases. Leukemia research, 25(9), 735–739.
• 22. Gur, H. D., Wang, S. A., Tang, Z., Hu, S., Li, S., Medeiros, L. J., & Tang, G. (2017). Clinical significance of isolated del(7p) in myeloid neoplasms. Leukemia research, 55, 18–22.
• 23. Medeiros, B. C., Kohrt, H. E., Arber, D. A., Bangs, C. D., Cherry, A. M., Majeti, R., Kogel, K. E., Azar, C. A., Patel, S., & Alizadeh, A. A. (2010). Immunophenotypic features of acute myeloid leukemia with inv(3)(q21q26.2)/t(3;3)(q21;q26.2). Leukemia research, 34(5), 594–597.
• 24. Nucifora G. (1997). The EVI1 gene in myeloid leukemia. Leukemia, 11(12), 2022–2031.
• 25. Poiré, X., Labopin, M., Polge, E., Volin, L., Finke, J., Ganser, A., Blaise, D., Yakoub-Agha, I., Beelen, D., Forcade, E., Lioure, B., Socié, G., Niederwieser, D., Labussière-Wallet, H., Maertens, J., Cornelissen, J., Craddock, C., Mohty, M., Esteve, J., & Nagler, A. (2020). The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA-matched allogeneic stem cell transplantation. American journal of hematology, 95(3), 282–294