Nové perspektivy v patogenezi a diagnostice lymfomu z plášťových buněk (mantle cell lymfomu)
| Title in English | New perspectives in the pathogenesis and diagnosis of mantle cell lymphoma |
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| Authors | |
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | Onkologie |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.onkologiecs.cz/pdfs/xon/2013/03/05.pdf |
| Field | Oncology and hematology |
| Keywords | mantle cell lymphoma; cyclin D1; t(11;14); SOX-11; NOTCH1 |
| Description | Mantle cell lymphoma represents about 7-8 % of all non-Hodgkin lymphomas. This entity is characterized by a combination of mostly aggresive clinical course and frequent relapses. The prognosis remains poor with a median overall survival of 4-5 years. It is hypothesized that a coincidence of several pathological events is necessary for arise of clinically manifest MCL. The primary oncogenic mechanism is considered to be a chromosomal translocation t(11;14) with juxtaposition of BCL1 gene to the IGH gene. It results in overexpression of cyclin D1, which positively affects the G1-S transition of cell cycle. Another frequent mutation is a deletion 11q22-23 leading to the inactivation of the ATM gene responsible for the DNA damage response. In such case, the genomic instability and subsequently the frequency of another mutations is highly increased. The gene expression profiling revealed many additional genetic alterations, such as constitutive activation of trancription factor NF-kappaB with anti-apoptotic effect or activation of mTOR system. Importantly, these pathways can be influenced by new targeted drugs (bortezomib, temsirolimus). Another secondary aberrations found in MCL are mutations in NOTCH1 gene and overexpression of neuronal transcription factor SOX11. However their significance for the pathogenesis and prognosis remains unclear. |