A novel t(1;8)(q25;p11.2) translocation associated with 8p11 myeloproliferative syndrome
Article first published online: 18 AUG 2011
© 2011 Blackwell Publishing Ltd
British Journal of Haematology
Volume 156, Issue 2, pages 271–273, January 2012
How to Cite
Yoshida, C., Takeuchi, M. and Sadahira, Y. (2012), A novel t(1;8)(q25;p11.2) translocation associated with 8p11 myeloproliferative syndrome. British Journal of Haematology, 156: 271–273. doi: 10.1111/j.1365-2141.2011.08839.x
- Issue published online: 22 DEC 2011
- Article first published online: 18 AUG 2011
- myeloproliferative disease;
- chromosomal rearrangements;
- lymphoid malignancies
The 8p11 myeloproliferative syndrome is an aggressive neoplasm characterized by a myeloproliferative neoplasm associated with eosinophilia and lymphadenopathy, usually involving T or B lineage lymphoblastic lymphoma/leukaemia. The hallmark of this disease is the reciprocal translocations involving the fibroblast growth factor receptor 1 gene (FGFR1) on chromosome 8p11 and different gene partners. Thus, in the current 2008 World Health Organization (WHO) classification (Bain et al, 2008), 8p11 myeloproliferative syndrome is designated as a ‘myeloid and lymphoid neoplasm with eosinophilia and abnormalities of FGFR1’. The most common gene partner is ZMYM2 on chromosome 13q12, and more than 10 other partners have been identified (Jackson et al, 2010; Wasag et al, 2011). We here describe the novel translocation of t(1;8)(q25;p11.2) associated with 8p11 myeloproliferative syndrome, which was detected using a spectral karyotyping (SKY) technique.
A 75-year-old woman with marked eosinophilia and lymphadenopathy was referred to us in September 2010. She had been under treatment for hypereosinophilic syndrome with hydroxycarbamide at another hospital from July 2009. Haematological examination revealed the following: haemoglobin 126 g/l, platelet count 180 × 109/l and leucocyte count 32.8 × 109/l, with 0.7% promyelocytes, 6.7% myelocytes, 2.7% metamyelocytes, 50.9% neutrophils, 6.3% lymphocytes, 13.7% monocytes, 16.7% eosinophils and 2.3% basophils. Mild elevation of the serum lactic dehydrogenase (243 u/l) was observed. The bone marrow was hypercellular, with 0.8% blasts, 5.0% promyelocytes, 9.6% myelocytes, 19.0% metamyelocytes, 40.2% neutrophils, 1.6% lymphocytes, 1.6% monocytes, 16.2% eosinophils and 5.8% erythroid precursors (Fig 1A). Computed tomographic examinations revealed cervical, supraclavicular, axillary, mediatinal, hilar, para-aortic, mesenteric and inguinal lymphadenopathy, splenomegaly and pleural effusion. An inguinal lymph node biopsy revealed disruption of the normal architecture of the lymph node and proliferation of high endothelial venules, with diffuse infiltration by small lymphoblasts. These cells were positive for CD3, CD79a, CD4, CD5, CD8 and TdT, but negative for CD25 and CD30 (Fig 1B–F). No eosinophil infiltration was noted in the lymph node specimen. Fluorescent in situ hybridization (FISH) was negative for the fusion genes FIP1L1-PDGFRA and BCR-ABL1. Chromosome analysis of the bone marrow cells on admission using G-banding stain alone mimicked those of a normal karyotype; however, reanalysis combined with SKY revealed the karyotype abnormality 46, XX, der(1)t(1;8)(q21;?), der(8)t(1;8)(q25;p11.2)del(8)(q?) in five out of 20 metaphases, and other 15 metaphases showed 46, XX (Fig 2A, B). Based on the above findings, we considered the diagnosis of this patient was 8p11 myeloproliferative syndrome. However, FISH analysis for the identification of FGFR1 breakpoints failed to demonstrate a disruption of the FGFR1 probe (Fig 2C).
The WHO classification diagnostic criteria for 8p11 myeloproliferative syndrome requires the demonstration of the translocation leading to FGFR1 rearrangement (Bain et al, 2008). The most frequent gene partner of FGFR1 is ZMYM2, followed in frequency by CNTRL, FGFR1OP and BCR (located on 9q33, 6q27 and 22q11, respectively); other minor partners have also been reported (Chaffanet et al, 1998; Demiroglu et al, 2001). The clinical and laboratory findings in this patient, such as lymphadenopathy (biopsied as biphenotypic lymphoblastic lymphoma), peripheral eosinophilia and bone marrow morphology consistent with myeloproliferative neoplasm, and cytogenetic analyses using both G-banding and SKY, which showed the translocation of t(1;8)(q25;p11.2), indicated the diagnosis of 8p11 myeloproliferative syndrome in this patient. However, FISH analysis did not confirm the FGFR1-rearrangement. Patnaik et al (2010) also reported a patient with a typical phenotype of 8p11 myeloproliferative syndrome and translocation of t(8;13)(p11.2;p10) who failed to demonstrate a FGFR1 rearrangement by FISH analysis. It is unknown whether our patient lacked the specific FGFR1-rearrangement or if FISH techniques failed to detect the underlying genetic abnormality in this case. However, we speculate that translocation of t(1;8)(q25;p11.2) led to the activation of FGFR1, and affected the pathogenesis of the tumour in this patient.
Any of the authors have no conflicts of interests to declare in connection with the submission of this paper.
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