The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase gene on chromosome 8p11-12. A new case of a 9-year-old boy with leukocytosis, eosinophilia, and general lymphadenopathy is reported in this study. Bone marrow examination showed eosinophilic hyperplasia, with blast cells amounting to 6-7%. Karyotyping revealed cytogenetic abnormalities, including t(8;9)(p11.2;q3?3). Fluorescence in situ hybridization for the FGFR1 gene rearrangement yielded positive results. Lymph node biopsy confirmed the diagnosis of precursor T-lymphoblastic lymphoma. The patient responded to chemotherapy, and unmatched related bone marrow transplantation was performed. A successful outcome was obtained with complete cytogenetic remission maintained for 14 months to date. In the future, FGFR1 inhibitors might be specific and effective therapeutic targets for EMS. Similar cases from the literature are reviewed.

Keywords:
8p11 myeloproliferative syndrome, Bone marrow transplantation, FGFR1 gene
1.
Abruzzo LV, Jaffe ES, Cotelingam JD, Whang-Peng J, Del Duca V Jr, Medeiros LJ: T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol 1992;16:236-245.
2.
Macdonald D, Sheerin SM, Cross NC, Spencer A, Goldman JM: An atypical myeloproliferative disorder with t(8;13) (p11;q12): a third case. Br J Haematol 1994;86:879-880.
3.
Macdonald D, Aguiar RC, Mason PJ, Goldman JM, Cross NC: A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: a review. Leukemia 1995;9:1628-1630.
4.
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.
5.
Bain BJ, Gilliland DG, Horny HP, Vardiman JW: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1; in Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. Geneva, WHO Press, 2008, pp 67-74.
6.
Gervais C, Dano L, Perrusson N, Helias C, Jeandidier E, Galoisy AC, Ittel A, Herbrecht R, Bilger K, Mauvieux L: A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm. Leukemia 2013;27:1186-1188.
7.
Jackson CC, Medeiros LJ, Miranda RN: 8p11 myeloproliferative syndrome: a review. Hum Pathol 2010;41:461-476.
8.
Morishige S, Oku E, Takata Y, Kimura Y, Arakawa F, Seki R, Imamura R, Osaki K, Hashiguchi M, Yakushiji K, Mizuno S, Yoshimoto K, Nagafuji K, Ohshima K, Okamura T: A case of 8p11 myeloproliferative syndrome with BCR-FGFR1 gene fusion presenting with trilineage acute leukemia/lymphoma, successfully treated by cord blood transplantation. Acta Haematol 2013;129:83-89.
9.
Tiong KH, Mah LY, Leong CO: Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers. Apoptosis 2013;18:1447-1468.
10.
Friedhoff F, Rajendra B, Moody R, Alapatt T: Novel reciprocal translocation between chromosomes 8 and 9 found in a patient with myeloproliferative disorder. Cancer Genet Cytogenet 1983;9:391-394.
11.
Lewis JP, Jenks H, Lazerson J: Philadelphia chromosome-negative chronic myelogenous leukemia in a child with t(8;9)(p11 or 12;q34). Am J Pediatr Hematol Oncol 1983;5:265-269.
12.
Oscier DG, Mufti GJ, Gardiner A, Hamblin TJ: Reciprocal translocation between chromosomes 8 and 9 in atypical chronic myeloid leukaemia. J Med Genet 1985;22:398-401.
13.
Jotterand Bellomo M, Muhlematter D, Wicht M, Delacretaz F, Schmidt PM: T(8;9)(p11;q32) in atypical chronic myeloid leukaemia: a new cytogenetic-clinicopathologic association? Br J Haematol 1992;81:307-308.
14.
Nakayama H, Inamitsu T, Ohga S, Kai T, Suda M, Matsuzaki A, Ueda K: Chronic myelomonocytic leukaemia with t(8;9)(p11;q34) in childhood: an example of the 8p11 myeloproliferative disorder? Br J Haematol 1996;92:692-695.
15.
van den Berg H, Kroes W, van der Schoot CE, Dee R, Pals ST, Bouts TH, Slater RM: A young child with acquired t(8;9)(p11;q34): additional proof that 8p11 is involved in mixed myeloid/t lymphoid malignancies. Leukemia 1996;10:1252-1253.
16.
Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pebusque MJ: FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33). Blood 2000;95:1788-1796.
17.
Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S, Parker S, Welborn J, Harris RI, Martinelli G, Montefusco V, Sinclair P, Wilkins BS, van den Berg H, Vanstraelen D, Goldman JM, Cross NC: Identification of four new translocations involving FGFR1 in myeloid disorders. Genes Chromosomes Cancer 2001;32:155-163.
18.
Yamamoto K, Kawano H, Nishikawa S, Yakushijin K, Okamura A, Matsui T: A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene. Eur J Haematol 2006;77:349-354.
19.
Mozziconacci MJ, Carbuccia N, Prebet T, Charbonnier A, Murati A, Vey N, Chaffanet M, Birnbaum D: Common features of myeloproliferative disorders with t(8;9)(p12;q33) and CEP110-FGFR1 fusion: report of a new case and review of the literature. Leuk Res 2008;32:1304-1308.
20.
Park TS, Song J, Kim JS, Yang WI, Song S, Kim SJ, Suh B, Choi JR: 8p11 myeloproliferative syndrome preceded by t(8;9)(p11;q33), CEP110/FGFR1 fusion transcript: morphologic, molecular, and cytogenetic characterization of myeloid neoplasms associated with eosinophilia and FGFR1 abnormality. Cancer Genet Cytogenet 2008;181:93-99.
21.
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;28:140-146.
22.
Yamamoto S, Ebihara Y, Mochizuki S, Kawakita T, Kato S, Ooi J, Takahashi S, Tojo A, Yusa N, Furukawa Y, Oyaizu N, Watanabe J, Sato K, Kimura F, Tsuji K: Quantitative polymerase chain reaction detection of CEP110-FGFR1 fusion gene in a patient with 8p11 myeloproliferative syndrome. Leuk Lymphoma 2013;54:2068-2069.
23.
Sarahx OJ, Anthony AO, Titilope AA, Alani SA: The 8p12 myeloproliferative syndrome. Niger Med J 2014;55:176-179.
24.
Xu LP, Chen Y, Shi HX, Huang XJ: 8p11 myeloproliferative syndrome cured by allogeneic hematopoietic stem cell transplantation: two case reports and literature review. Beijing Da Xue Xue Bao 2013;45:993-996.
25.
Egawa T, Tillman RE, Naoe Y, Taniuchi I, Littman DR: The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med 2007;204:1945-1957.
26.
Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC, Komori T, Ito Y, Littman DR: Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 2002;111:621-633.
27.
Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL: Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011;364:2496-2506.
28.
Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J, Alpermann T, Haferlach C, Haferlach T: RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood 2011;117:2348-2357.
29.
Greif PA, Konstandin NP, Metzeler KH, Herold T, Pasalic Z, Ksienzyk B, Dufour A, Schneider F, Schneider S, Kakadia PM, Braess J, Sauerland MC, Berdel WE, Buchner T, Woermann BJ, Hiddemann W, Spiekermann K, Bohlander SK: RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes. Haematologica 2012;97:1909-1915.
30.
Buijs A, van Wijnen M, van den Blink D, van Gijn M, Klein SK: A ZMYM2-FGFR1 8p11 myeloproliferative neoplasm with a novel nonsense RUNX1 mutation and tumor lysis upon imatinib treatment. Cancer Genet 2013;206:140-144.
31.
Yamamoto S, Otsu M, Matsuzaka E, Konishi C, Takagi H, Hanada S, Mochizuki S, Nakauchi H, Imai K, Tsuji K, Ebihara Y: Screening of drugs to treat 8p11 myeloproliferative syndrome using patient-derived induced pluripotent stem cells with fusion gene CEP110-FGFR1. PLoS One 2015;10:e0120841.
32.
Chase A, Grand FH, Cross NC: Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome. Blood 2007;110:3729-3734.
33.
Wasag B, Lierman E, Meeus P, Cools J, Vandenberghe P: The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(Q22;P11). Haematologica 2011;96:922-926.
34.
Lierman E, Smits S, Cools J, Dewaele B, Debiec-Rychter M, Vandenberghe P: Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases. Leukemia 2012;26:1693-1695.
35.
Chase A, Bryant C, Score J, Cross NC: Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome. Haematologica 2013;98:103-106.
36.
Ren M, Qin H, Ren R, Cowell JK: Ponatinib suppresses the development of myeloid and lymphoid malignancies associated with FGFR1 abnormalities. Leukemia 2013;27:32-40.
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