Deregulated expression of NKL homeobox genes in T-cell lymphomas.

摘要: Recently, we have presented a scheme, termed "NKL-code", which describes physiological expression patterns of NKL homeobox genes in early hematopoiesis and lymphopoiesis including main stages T-, B- NK-cell development. Aberrant activity these underlies the generation hematological malignancies notably T-cell leukemia. Here, searched for deregulated entities lymphomas comprising angioimmunoblastic lymphoma (AITL), anaplastic large cell (ALCL), adult leukemia/lymphoma (ATLL), hepatosplenic (HSTL), NK/T-cell (NKTL) peripheral (PTCL). Our data revealed altogether 19 aberrantly overexpressed types, demonstrating involvement as well. For detailed analysis focused on gene MSX1 is normally expressed NK-cells. was subsets HSTL patients HSTL-derived sister lines DERL-2 DERL-7 served models to characterize mechanisms deregulation. We performed karyotyping, genomic profiling, whole genome sequencing reveal mutated candidates, fusion CD53-PDGFRB. Subsequent knockdown experiments allowed reconstruction an aberrant network involved deregulation, chromatin factors AUTS2 histone HIST1H3B(K27M). The encoding located at chromosome 7q11 may represent basic target hallmark aberration i(7q). Taken together, our findings highlight oncogenic role identify novel player HSTL, implicated NK- differentiation.