New Сytogenetic Approaches in Patients with Primary Myelofibrosis

MYELOID TUMORS , ,

TL Gindina, NN Mamaev, VV Baikov, MV Barabanshchikova, EN Nikolaeva, IA Petrova, IS Moiseev, OV Pirogova, YuYu Vlasova, MO Ivanova, EV Morozova, SN Bondarenko, BV Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: + 7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Baikov VV, et al. New Сytogenetic Approaches in Patients with Primary Myelofibrosis. Clinical oncohematology. 2016;9(1):61–9 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-61-69

ABSTRACT

Aim. To evaluate the potential of a new cytogenetic technique in patients with primary myelofibrosis (PMF).

Materials and methods. 48-hour blood cell cultures (according to Singh et al., 2013) were used for cytogenetic study in 11 PMF patients (5 female, 6 men, aged 32–60 years; median 48.6 years). GTG-banding and different types of fluorescence in situ hybridization (FISH) techniques were used for identification of chromosomal aberrations.

Results. The incidence of abnormal karyotypes in blood cultures was significantly higher than that in standard bone marrow cultures (82 vs 27 %; p < 0.01). The polyploid clones were found in blood cultures of 45 % of patients. Structural chromosomal aberrations were found in chromosomes 6, 1, 3, as well as 16 and 17 (in 2 and 1 patients with each aberration, respectively). In all but one patients these abnormalities in diploid and polyploid metaphases were identical. Partial 1q trisomy resulted from adding of additional (1q21–1q44) material translocated to the short arm of chromosome 5 to the material of 2 normal homologue of chromosome 1. It seems that 1q+, i(17q) and some others chromosomal abnormalities were secondary, whereas 6p21 locus involvement may be a primary defect in PMF. The t(3;6)(q25;p21) translocation described for the first time and confirmed by FISH should be considered a variant of well-known translocation t(1;6). Allo-HSCT in 2 patients with 1q+ was successful, whereas there were problems with engraftment in a female patient with prognostically unfavorable t(3;3)(q21;q26) translocation associated with the EVI1 gene overexpression.

Conclusion. Cytogenetic examinations in blood cultures provide important additional information about PMF patients.

Keywords: primary myelofibrosis, 48-hour peripheral blood cell culture, cytogenetics.

Received: July 14, 2015

Accepted: November 1, 2015

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REFERENCES

  1. Heuck G. Zwei Falle von Leukamie mit eigenthumlichem Blut-resp Knochenmarkbefund. Archiv fur pathologische Anatomie und Physiologie und fur klinische Medicin. 1879;78(3):475–96. doi: 10.1007/bf01878089.
  2. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6(4):372–5.
  3. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369:2379–90. doi: 10.1056/nejmoa1311347.
  4. Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28:1472–7. doi: 10.1038/leu.2014.3.
  5. Panagiota V, Thol F, Markus B, et al. Prognostic effect of calreticulin mutations in patients with myelofibrosis after allogeneic hematopoetic stem cell transplantation. Leukemia. 2014;28:1552–5. doi: 10.1038/leu.2014.66.
  6. Komrokji RS, Seymour JF, Roberts AW, et al. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2 (V617F) inhibitor, in patients with myelofibrosis. Blood. 2015;125(17):2649–55. doi: 10.1182/blood-2013-02-484832.
  7. Hoffman R, Rondalli D. Biology and treatment of primary myelofibrosis. Hematology (Am Soc Hematol Educ Program). 2007:346–54. doi: 10.1182/asheducation-2007.1.346.
  8. Geraedts JP, den Ottolander GJ, Ploem JE, Muninghe OG. An identical translocation between chromosome 1 and 7 in three patients with myelofibrosis and myeloid metaplasia. Br J Haematol. 1980;44:569–75. doi: 10.1111/j.1365-2141.1980.tb08711.x.
  9. Bernstein R, Pinto MR, Behr A, Mendelow B. Chromosome 3 abnormalities in acute non-lymphocytic leukemia (ANLL) with abnormal thrombopoiesis: report of three patients with a “new” inversion anomaly and a further case of homologous translocation. Blood. 1982;60:613–7.
  10. Clare N, Elson D, Mannhof L. Cytogenetic studies of peripheral myeloblasts and bone marrow fibroblasts in acute myelofibrosis. Am J Clin Pathol. 1982;77:762–6. doi: 10.1093/ajcp/77.6.762.
  11. Borgstrom GM, Knutila S, Ruutu T, et al. Abnormalities of chromosome 13 in myelofibrosis. Scand J Haematol. 1984;33:15–21.
  12. Miller JB, Testa JR, Lindgren V, Rowley JD. The pattern and clinical significance of karyotypic abnormalities in patients with idiopathic and postpolycythemic myelofibrosis. Cancer. 1985;55:582–91. doi: 10.1002/1097-0142(19850201)55:3<582::aid-cncr2820550318>3.0.co;2-o.
  13. Castoldi G, Cuneo A, Tomasi P, Ferrari L. Chromosome abnormalities in myelofibrosis. Acta Haematol. 1987;78(Suppl. 1):104–8. doi: 10.1159/000205913.
  14. Smadja N, Krulik M, de Gramount A, et al. Cytogenetic studies in twelve patients with primary myelofibrosis and myeloid metaplasia. Cancer Genet Cytogenet. 1987;24:151–8. doi: 10.1016/0165-4608(87)90092-6.
  15. Demory JL, Dupriez B, Fenaux P, et al. Cytogenetic studies and their prognostic significance in agnogenic myeloid metaplasia: a report of 47 cases. Blood. 1988;72:855–9.
  16. Djordjevic V, Dencic-Fekete M, Jovanovic J, et al. Cytogenetics of agnogenic myeloid metaplasia: a study of 61 patients. Cancer Genet Cytogenet. 2007;173:57–62. doi: 10.1016/j.cancergencyto.2006.09.02.
  17. Hidaka K, Shide K, Shimoda H, et al. The impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis: a prospective survey of 202 cases in Japan. Eur J Haematol. 2009;83:328–33. doi: 10.1111/j.1600-0609.2009.01298.x.
  18. Hussein K, Van Dyke DL, Tefferi A. Conventional cytogenetics in myelofibrosis: literature review and discussion. Am J Hematol. 2009;82:329–38. doi: 10.1111/j.1600-0609.2009.01224.x.
  19. Caramazza D, Begna KH, Gangar N, et al. Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients. Leukemia. 2011;25:82–8. doi: 10.1038/leu.2010.234.
  20. Tefferi A, Lasho TL, Jimma Th, et al. One thousand patients with primary myelofibrosis: The Mayo clinic experience. Mayo Clin Proc. 2012;87(1):25–33. doi: 10.1016/j.mayocp.2011.11.001.
  21. Wassie E, Finke Ch., Gangat N, et al. A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients. Br J Haematol. 2014; doi: 10.1111/bjh.132. doi: 10.1111/bjh.13260.
  22. Li B, Xu J, Li Ch, et al. Cytogenetic studies and their prognostic contribution in 565 Chinese patients with primary fibrosis. Am J Hematol. 2014;89(11):1043–7. doi: 10.1002/ajh.23824.
  23. Абдулкадыров К.М., Шуваев В.А., Мартынкевич И.С. Первичный миелофиброз: собственный опыт и новое в диагностике и лечении. Онкогематология. 2015;10(2):26–36.
    [Abdulkadyrov KM, Shuvaev VA, Martynkevich IS. Primary myelofibrosis: own experience and news from diagnostic and treatment. Onkogematologiya. 2015;10(2):26–36. (In Russ)]
  24. Singh NR, Morris ChM, Koleth M, et al. Polyploidy in myelofibrosis: analysis by cytogenetic and SNP indicates association with advancing disease. Mol Cytogenet. 2013;6:59–71. doi: 10.1186/1755-8166-6-59.
  25. Devine SM, Hoffman R, Verma A, et al. Allogeneic blood cell transplantation following reduced-intensity conditioning is effective therapy for older patients with myelofibrosis with myeloid metaplasia. Blood. 2002;99:2255–8. doi: 10.1182/blood.v99.6.2255.
  26. Kroger N, Zabelina T, Schieder H, et al. Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis. Br J Haematol. 2005;128:690–7. doi: 10.1111/j.1365-2141.2005.05373.x.
  27. Merup M, Lazarevic V, Nahi H, et al. Different outcome of allogeneic transplantation in myelofibrosis using conventional or reduced-intensity conditioning regimens. Br J Haematol. 2006;135:367–73. doi: 10.1111/j.1365-2141.2006.06302.x.
  28. Kroger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2009;114:5264–70. doi: 10.1182/blood-2009-07-234880.
  29. Schaffer LG, McGovan-Jordan J, Schmid M. ISCN. An international System for Human Cytogenetic Nomenclature. Basel: S. Karger; 2013.
  30. Tefferi A, Dingli D, Li C, Dewald GW. Prognostic diversity among cytogenetic abnormalities in myelofibrosis with myeloid metaplasia. Cancer. 2005;104:1656–60. doi: 10.1002/cncr.21358.
  31. Strasser-Weiple K, Steurer M, Kees M, et al. Chromosome 7 deletions are associated with unfavorable prognosis in myelofibrosis and myeloid metaplasia. Blood. 2005;105(10):4146. doi: 10.1182/blood-2004-11-4319.
  32. Hussein K, Huang J, Lasho T, et al. Karyotype complements the International Prognostic Scoring System for primary myelofibrosis. Eur J Haematol. 2009;82:256–9. doi: 10.1111/j.1600-0609.2009.01216.x.
  33. Hussein K, Pardanani AD, Van Dyke DL, et al. International Prognostic Scoring System-independent cytogenetic risk categorization in primary myelofibrosis. Blood. 2010;115:496–9. doi: 10.1182/blood-2009-08-240135.
  34. Gangat N, Caramazza D, Vaidya R, et al. DIPSS Plus: a refined dynamic international prognostic scoring system for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29(4):392–7. doi: 10.1200/jco.2010.32.2446.
  35. Vaidya R, Caramazza D, Begna KH, et al. Monosomal karyotype in primary myelofibrosis is detrimental to both overall and leukemia-free survival. Blood. 2011;117(21):5612–5. doi: 10.1182/blood-2010-11-320002.
  36. Huret JL. Atlas of Genetics and Cytogenetics in Oncology and Haematology. Poitiers: University Hospital; 2011. p. 5. doi: 10.4267/2042/44590.