A rare case of myeloproliferative disease with t(8;13)(p11;q12) associated with eosinophilia and lymphadenopathy


Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8р11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.


  1. Bain BJ, Gulliland DG, Horny P, Vardiman JW. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. In: Swerdlow SH, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008:68-73.
  2. Abruzzo LV, Jaffe ES, Cotelingam JD, Whang-Peng J, Del Duca Jr V, Medeiros LJ. T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol. 1992;16(3):236-245.
  3. Inhorn RC, Aster JC, Roach SA, Slapak CA, Soiffer R, Tantravahi R, Stone RM A syndrome of lymphoblastic lymphoma, eosinophilia and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): description of a distinctive clinicopathologic entity. Blood. 1995;85,1881-1887.
  4. Macdonald D, Aguiar IC, Mason PJ, Goldman JM, Cross NC. A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: a review. Leukemia. 1995;9(10): 1628-1630.
  5. Heath C, Cross NC. Critical role of STAT 5 activation in transformationmediated by XNF 198-FGFR1. J Biol Chem. 2004;279: 6666-6673.
  6. Goradia F, Bayert M, Cornfield D. The 8p 11 myeloproliferative syndrome. Review of literature and an illustrative case report. Int J Clin Exp Pathol. 2008;1:448-456.
  7. Malli T, Buxhofer-Ausch V, Rammer M, Erdel M, Kranewitter W, Rumpold H, Marschon R, Deutschbauer S, Simonitsch-Klupp I, Valent P, Muellner-Ammer K6, Sebesta C, Birkner T, Webersinke G. Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome. Genes Chromosomes Cancer. 2015 Sep 22. doi: 10.1002/gcc.22311
  8. Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum Pathol. 2010;41(4):461-476.
  9. Catovsky D, Bernasconi C, Verdonck PJ, Postma A, Hows J, van der Does-van den Berg AJK, Ree H, Castelli G, Morra E, Galton DAG. The association of eosinophilia with lymphoblastic leukemia or lymphoma: a study of seven patients. Br J Haematol. 1980;45(4):523-534.
  10. Friedhoff F, Rajenda B, Moody R, Alapatt T. Novel reciprocal translocation between chromosome 8 and 9 found in a patient with myeloproliferative disorder. Cancer Genet Cytogenet. 1983;9(4): 391-394.
  11. Hu S, He Y, Zhu X, Li J, He H. Myeloproliferative Disorders with t(8;9) (p12;q33): a case report and review of the literature. Pediatr Hematol Oncol. 2011;28(2):140-146.
  12. Posner MR, Said J, Pinkus GS, Nadler LM, Hardy R, Flatow F, Skarin AT. T-cell lymphoblastic lymphoma with subsequent acute nonlymphocytic leukemia: a case report. Canсer. 1982;50(1): 118-124.
  13. Гиндина Т.Л., Мамаев Н.Н., Байков В.В., Бархатов И.М., Горбунова А.В., Бондаренко С.Н., Слесарчук О.А., Аверьянова М.Ю., Успенская О.С., Афанасьев Б.В. Два новых наблюдения 8р11 миелопролиферативного синдрома с транслокациями t(6;8)(q27;p11) и t(8;9)(p11;q34), делецией гена FGFR1 и гиперэкспрессией генаEVI-1: теоретические и клинические аспекты. Гематология и трансфузиология. 2013; 58(4):13-17.
  14. Jotterand Bellomo M, Muhlematter D, Wicht M, Delacretaz F, Schmidt PM. t(8;9)(p11;q32) in atypical chronic myeloid leukemia:a new cytogenic-clinicopathologic association? Br J Hematol. 1992;81(2):307-308.
  15. Nakayama H, Inamitsu T, Ohga S, Kai T, Suda M, Matsuzaka A, Ueda K. Chronic myelomonocytic leukemia with t(8;9)(p11;q34) in childhood:an example of the 8p 11 myeloproliferative disorder? Br J Hematol. 1996;92(3):692-695.
  16. Popovici C, Zhang B, Gregoire MJ, Jonveaux P, Lafage-Pochitaloff M, Birnbaum D, Pébusque M-J. The t(6;8)(q27;p11)translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1. Blood. 1999;93(4):1381-1389.
  17. Asuman Demirogly A, Steer EJ, HeathC, Asuman Demiroglu, E Joanna Steer, Carol Heath, Kerry Taylor, Mark Bentley, Steven L. Allen, Prasad Koduru, Judith P. Brody, Geoffrey Hawson, Robyn Rodwell, Mary-Lou Doody, Fernando Carnicero, Andreas Reiter, John M. Goldman, Junia V Melo and Nicholas CP. Cross The t (8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGRF1 fusion proteins. Blood. 2001;98:3778-3783.
  18. Heiss S, Erdel M, Gunsilius E, Nachbaur D, Tzankovet A. Myelodysplastic/myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24) first description of case. Hum Pathol. 2005;36(10): 1148-1151.
  19. Chaffanet M, Popovici C, Leroux D. t(6;8),t(8;9), and t(8;13)translocations associated with stem cell myeloproliferative disorders have close of identical breakpoints in chromosome region 8p-11-12. Oncogene. 1998;16(7):945-949.
  20. Chase A, Bryant J, Score J, Cross NCP. Ponatinib as targeted therapy for FGFR1 fusions associated with thе 8p11 myeloproliferative syndrome. Haematologica. 2013;98(1):103-106.
  21. Mingqiang Ren, Mei Hong, Gentao Liu, Hongjin Wang, Vijay Patel, Paul Biddinger, Jeane Silva, John Cowell, Zhonglin Hao Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR.1 Oncol Reports. 2013;29(6):2181-2190. doi: 10.3892/or.2013.2386
  22. Chase A, Bryant C, Score J, Cross NC. Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome Haematologica. 2013;98(1):103-106.
  23. Федянин М.Ю., Хмелькова Д.Н., Серебрийская Т.С., Никольская Т.А., Тюляндин С.А. Перспективы терапевтического воздействия на сигнальный путь FGFR. Успехи молекулярной онкологии. 2015;2(1):27-37.
  24. Mingqiang Ren, Haiyan Qin, Ruizhe Ren, Josephine Tidwell, and John K. Cowell. Src Activation Plays an Important Key Role in Lymphomagenesis Induced by FGFR1 Fusion Kinases. Cancer Res. 2011;71:7312-7322.
  25. Wakim JJ, Tirado CA, Chen W, Collins R. t(8;22)/BCR-FGFR1 myeloproliferative disorder presenting as B-acute lymphoblastic leukemia: report of a case treated with sorafenib and review of the literature. Leuk Res. 2011;35(9):e151-153.
  26. Chen J, DeAngelo DJ, Kutok JL, Williams IR, Lee BH, Wadleigh M, Duclos N, Cohen S, Adelsperger J, Okabe R, Coburn A, Galinsky I, Huntly B, Cohen PS, Meyer T, Fabbro D, Roesel J, Vanerji L, Griffin JD, Sheng Xiao, Fletcher JA, Stone RM, Gilliland DG. PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Proc Natl Acad Sci USA. 2004;101(40):14479-14484.
  27. Photis Beris, Monika Nagy, Daniel Robert, Kaveh Samii, Tom McKee, Jovita Schuler. Compassionate Use of Midostaurin in Myeloid and Lymphoid Neoplasia with FGFR1 Abnormality. Case Reports in Clinical Medicine. 2014;3:560-565.
  28. Khodadoust M, Luo B, Medeiros C. Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed phenotype acute leukemia. Leukemia. 2015. doi: 10.1038/leu.2015.136
  29. Gotlib J. Tyrosine Kinase Inhibitors and Therapeutic Antibodies in Advanced Eosinophilic Disorders and Systemic Mastocytosis. Curr Hematol Malig Rep. 2015 Sep 24.
  30. Rao PN, CesarmanG, Coleman M. Cytogenetic evidence for extramedullary blast crisis with t(8;13)(q11;p11) in chronic myelomonocytic leukemia. Acta Hematol. 1992;88:201-203.
  31. Cross NC, Reiter A. Fibroblast growth factor receptor and platelet-derived growth factor receptor abnormalities in eosinophilic myeloproliferative disorders. Acta Haematol. 2008;119(4):199-206.
  32. Klion AD. Eosinophilic Myeloproliferative Disorders. ASH Education Book December 10, 2011 vol. 2011 no. 1257-1263.
  33. Dolan M, Cioc A, Cross NC, Neglia JP, Tolar J. Favorable outcome of allogenic hematopoietic cell transplantation for 8p 11 myeloproliferative syndrome with BCR-FGFR 1 gene fusion. PediatrBlood Cancer. 2012;59(1):194-196. doi: 10.1002/pbc.23404
  34. Havelange V, Demoulin J-B. Review of current classification, molecular alterations, and tyrosine kinase inhibitor therapies in myeloproliferative disorders with eosinophilia. J Blood Med. 2013;4:111-121.
  35. Михайлова Н.Б., Афанасьев Б.В. Клональные эозинофилии. Клиническая онкогематология. 2009;2(1):1-10.

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