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. 2018 May 17;131(20):2262-2266.
doi: 10.1182/blood-2018-01-830968. Epub 2018 Mar 28.

Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract

Ayush Sharma  1 , Naoki Oishi  2   3 , Rebecca L Boddicker  2 , Guangzhen Hu  2 , Hailey K Benson  2 , Rhett P Ketterling  2 , Patricia T Greipp  2 , Darlene L Knutson  2 , Sara M Kloft-Nelson  2 , Rong He  2 , Bruce W Eckloff  4 , Jin Jen  2 , Asha A Nair  5 , Jaime I Davila  5 , Surendra Dasari  5 , Konstantinos N Lazaridis  1   6 , N Nora Bennani  7 , Tsung-Teh Wu  2 , Grzegorz S Nowakowski  6   7 , Joseph A Murray  1 , Andrew L Feldman  2
Affiliations

Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract

Ayush Sharma et al. Blood. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract with STAT3-JAK2 fusion. (A-B) Duodenal biopsy shows a monotonous population of small lymphocytes in the lamina propria with preservation of the glands (hematoxylin and eosin stain; patient 2; original magnification ×40 [A] and ×400 [B]). By immunohistochemistry, the cells are positive for (C) CD3 and (D) CD4 and negative for (E) CD8 (original magnification ×400 [C-E]). (F) FISH using a break-apart probe to the JAK2 gene region shows separations of red and green signals, indicating the presence of a rearrangement (original magnification ×600). (G) FISH using a dual-fusion probe for the STAT3 (red) and JAK2 (green) gene regions shows red-green fusion signals (f), indicating the presence of fusion of these 2 regions (original magnification ×600). (H) RNA sequencing identifies chimeric reads supporting the presence of STAT3-JAK2 fusion joining the end of exon 23 of STAT3 with the beginning of exon 17 of JAK2. The identical breakpoint was found in all 3 patients who had GI TLPD with STAT3-JAK2 fusion whose samples were successfully sequenced. (I) Sanger sequencing confirms the STAT3-JAK2 breakpoint identified by RNA sequencing. (J) Protein domain structure of STAT3, JAK2, and predicted STAT3-JAK2 fusion protein. The amino acid numbers at the breakpoints are shown as well as the location of STAT3Y705. Using immunohistochemistry showed that the cells lack staining for (K) pSTAT3Y705 but are positive for (L) pSTAT5Y694 (patient 2; original magnification ×1000). CCD, coiled coil domain; DBD, DNA binding domain; FERM, four-point-one, ezrin, radixin, moesin homology domain; JH1, JAK homology 1 (tyrosine kinase) domain; JH2, JAK homology 2 (pseudokinase) domain; LD, linker domain; NTD, N-terminal domain; SH2, Src homology 2 domain; TAD, transcription activation domain.
See this image and copyright information in PMC

References

    1. Jaffe ES, Chott A, Ott G, et al. . Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. In: Swerdlow SH, Camp E, Harris NL, et al., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer; 2017:379-380.
    1. Perry AM, Warnke RA, Hu Q, et al. . Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood. 2013;122(22):3599-3606. - PMC - PubMed
    1. Mansoor A, Pittaluga S, Beck PL, Wilson WH, Ferry JA, Jaffe ES. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood. 2011;117(5):1447-1452. - PMC - PubMed
    1. Smith CA, Fan G. The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms. Hum Pathol. 2008;39(6):795-810. - PubMed
    1. Lacronique V, Boureux A, Valle VD, et al. . A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science. 1997;278(5341):1309-1312. - PubMed

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