A novel nude mice model of human extranodal nasal type NK/T-cell lymphoma

Abstract

A novel nude mice model of human extranodal nasal type NK/Tcell lymphoma was established by subcutaneously implanting the sample taken from the patient with secondary extranodal nasal type NK/T-cell lymphoma of the stomach into the right axillary region of a BALB/c (nu/nu) nude mouse. This model had been successfully transplanted in vivo for thirty-two generations with a stable growth cycle. The survival rates of both resuscitation and transplantation were 100%. Histologically, the tumor cells were medium to large size and arranged in sheets, with a little mesenchyma, and disseminated almost in all passages of the lymphoma-bearing nude mice. Immunologically, the tumor cells were positive for CD56, cytoplasmic CD3, granzyme B or TIA-1 and LMP1, sometimes for CD8 but negative for surface CD3, CD7, CD20 and CD1a. EBER1/2 was found. No T-cell receptor c gene rearrangement was detected in the transplanted tumors. Furthermore, both human sequencing-tagged sites SY14 and Y chromosome were detected by PCR or fluorescent in situ hybridization, respectively, in the transplanted tumor. The transplanted tumor in this novel nude mice model maintained the essential features of human extranodal nasal type NK/T-cell lymphoma, and it would be an ideal tool in vivo for further research of the tumor.

STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma

“…T-cell receptor-g and immunoglobulin H (Framework region (Fr)1, Fr2 and Fr3]) loci were in the germinal conformation. Cytogenetical analysis disclosed a near tetraploid pattern with a complex formula with numerous numerical and structural chromosome changes as follows: 50-82, ÀXx4 [13],À3 [12], add(3)(p?24) [3], À4 [12], À5 [12], del(6)(q12) [2], þ del(6)(q12) [11], add(6)(q26) [11], del(7)(p1?2p1?5) [9], add(7)(p1?2) [7], À7 [4], À8, À8 [12], À9 [3], À9, À9 [10], À10, À10 [13], À11 [13], add(11)(p11) [4], þ add(11)(p11) [8], add(11)(q22) [10], þ add(11) (q22) [2], À12 [9], À13 [11], À14 [3], À15 [4], À16, [3], À17 [4], À17, À17 [8], add(18)(p11) Â 2 [13], þ 20 [3], þ mar1 [12], þ 1-7mars [11] cp [13]. As some structural abnormalities are present in duplicate, they occurred before endoreduplication, probably as some numerical one, whereas some others obviously occurred as secondary events (Figure 2b).…”

“…5 However, the mechanisms involved in the pathogenesis and resistance to treatment still remain poorly understood, and the deep research for this special tumor has been hampered by its rarity and insufficient supply of the tumoral samples. 12 Indeed, only a very small number of bona fide NK leukemia-lymphoma cell lines have been described in detail [13][14][15][16] (for review, see Drexler and Matsuo 17 ).…”

Selective drug combination vulnerabilities in STAT3- and TP53-mutant malignant NK cells

“…No primary patient cell culture systems have been documented. Only a handful of xenograft mouse models from cell lines 66,67 and one single case of a patient-derived xenograft model from a patient with NKTCL 68 have been described, and they all tend to be unstable models, questioning their relevance.…”

Extranodal NK/T-Cell Lymphoma: Toward the Identification of Clinical Molecular Targets

“…Before settingup clinical trials, extensive experimental validation of the potential target will have to be undertaken using the available models. In this respect, the study of tumor engrafting and development in immunocompromised mice injected with NKTCL cell lines or tumor fragments [82, 109] can be valuable models to test new potential drugs and their in vivo activity. One can hope that the efforts of the researchers working to understand this pathology will soon lead to progress in the treatment of these lymphomas.…”