mantle cell lymphoma prognosis | The mantle cell lymphoma: from diagnosis to Outlook Therapeutiquesmantle cell lymphoma: year overview from diagnosis to future therapies

The mantle cell lymphoma: from diagnosis to Outlook Therapeutiquesmantle cell lymphoma: year overview from diagnosis to future therapies

Summary
The lymphoma cells of the mantle (LCM) is part of no hodgkiniens (LMNH) malignant lymphomas. Tumor cell expresses classically a phenotype CD19, CD20 +, CD5 +, CCND1, + CD10−, CD23−, Bcl - 2 + with a surface immunoglobulin (usually IgM type). The other feature of the LCM is the presence of a translocation between chromosomes 11 and 14. The t (11; 14) positions the CCND1 gene under the dependence of the gene encoding the immunoglobulin heavy chain. The consequence is the increase in the expression of the protein cyclin D1 inducing the dysregulation of the cell cycle. In addition to the classic form, there are histological variants (Nodular or diffuse) forms, cytologic (classic form, in small cells or blast), phenotypic, cytogenetic (absence of t (11; 14)), or even clinical (tumor shape or) no tumor). The LCM is approximately 5% of the LMNH but its incidence is increasing. The median age at diagnosis is 68 years with a male. At diagnosis, the MTR extension is a stage III - IV in the Ann Arbor classification in more than 80% of patients. Digestive and spinal cord damage is frequent. Splenomegaly is present in half of the cases and the tumor masses are happy to large. The pejorative nature of the blast variant is found in most of the studies. The median survival has increased substantially in recent years from four to six in less than ten years thanks to the use of the high-dose chemotherapy with autologous for younger patients stem cell transplant. However, relapse remains the rule. The recent establishment of an index specific to the LCM prognosis could adapt the treatment. The growing place of monitoring of residual disease by molecular biology techniques is already discussing the preemptive treatment of relapse. Targeted therapies (avenues of transduction, inhibitor of the proteasome inhibitor, molecules targeting proteins in apoptosis, immunotherapy, radio-immunotherapy...) used alone or in combination with chemotherapy already open new therapeutic perspectives. In the coming years, therapeutic progress will probably come from a better understanding of oncogenesis allowing the identification of new therapeutic targets.

Abstract
Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma (NHL) entity. The translocation between chromosomes 11 and 14 is the hallmark of MCL cytogenetics. This translocation leads to the dysregulation of the CCDN1 gene, and overexpression of cyclin D1 which promotes cell cycling. Despite has classical phenotype (CD19 +, CD20 +, CD5 +, + CCND1, CD10−, CD23−, Bcl - 2 +, Ig at the membrane, mainly IgM), MCL is not a homogeneous disease and several cytological, phenotypic, cytogenetic and clinical variants have been described. MCL represents 5% of NHLs with its incidence constantly increasing over the last years. Median age at diagnosis is 68 years. Stage III - IV disease is observed in more than 80% of patients at presentation, with intestinal and bone marrow being the most frequently involved organs, while the spleen is enlarged in half of cases. Intensive strategies including high-dose chemotherapy followed by autologous stem cell transplantation have significantly improved the outcome of MCL patients. Median overall survival rate increased from 3 to 5 years during the last decade. At present, induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant is the standard regimen in younger patients. However, most of MCL patients will experience relapse. Thus, close monitoring of minimal residual disease (currently under assessment) may represent a valuable tool for assessment of disease response during follow up. Future innovative therapies that are being presently investigated in prospective trials include transduction pathways inhibitors, proteasome inhibitors, pro-apoptotic molecules, immunotherapy and/or radiolabeled immunotherapy, and will likely open a new era for targeted therapies in MCL.