mantle cell lymphoma | Mantle cell lymphoma

Mantle cell lymphoma

Summary
Mantle cell lymphoma (LCM) is a B-phenotypic non-Hodgkin's lymphoma (LMNH) derived from a naive pre-centre germ cell. The presence of a translocation between chromosomes 11 and 14 (t (11; 14)) is the cytogenetic characteristic of this hemopathy but is not specific [1]. Progressively individualized from other LMNH in the years 1990, the LCM corresponds to a specific cytological, phenotypic and genetic entity, the characteristics of which are specified in the latest version of the WHO classification. The therapeutic management of this malignant hemopathy, considered to be aggressive, has progressively evolved in recent years to distinguish itself from other LMNH, where the importance of the correct diagnosis. These nosological and then therapeutic evolutions have been accompanied by a progression of knowledge about ontogeny, oncogenesis and the biology of this lymphoma. Despite great progress, the LCM remains a pathology considered incurable, so therapeutic progress is still needed.


7 Mantle cell lymphoma
S. Le Gouill, A. Moreau
S. Le Gouill (
) – Clinical Hematology Service, CHU de Nantes, Place Alexis Ramage,
44093 Nantes Cedex 1
E-mail: steven.legouill@chu-nantes.fr
A. Moreau – Department of Anatomy Pathology of the CHU of Nantes
Under the direction of Pauline Brice and Catherine Taylor, therapeutic News in the
Lymphoma.
ISBN: 978-2-8178-0370-8, © Springer-Verlag Paris 2013
Introduction
Mantle cell lymphoma (LCM) is a malignant lymphoma not
B-phenotypic Hodgkin's (LMNH) deriving from a naive pre-centre cell
Germ. The presence of a translocation between chromosomes 11 and 14
(t (11; 14)) is the cytogenetic characteristic of this hemopathy, but it
is not specific [1]. Progressively individualized from other LMNH
In the years 1990, the LCM corresponds to a particular entity in the plan
Phenotypic and genetic, the characteristics of which are specified in the
In the latest version of the WHO classification. The support
Therapeutic of this malignant hemopathy, considered aggressive, has
Progressively evolved in recent years to distinguish itself from other
LMNH, hence the importance of asking the right diagnosis. These developments nosological
Then therapeutic went along with a progression of knowledge
Affecting the ontogeny, the oncogenesis and all the biology of this lymphoma.
Despite great progress, the LCM remains a pathology considered to be
Incurable, therapeutic progress is still necessary.
Epidemiology
The LCM represents between 5 and 10% of the LMNH. Its prevalence varies according to
The age of 0.5 to 3 cases for 100 000 inhabitants per year [2]. In France, a study
Epidemiological study from the three cancer registries specialized in the 104 therapeutic news in Lymphomas
Hemic Malignant (Register of the Côte-d'or, Basse-Normandie and register
of Gironde) counted 135 cases between 2002 and 2006, i.e. a rate of incidents
Standardized for 100 000 inhabitants of 0.72 for men, compared with 0.17 at
Women. This study found a male to female ratio close to 4. There is,
To date, no explanation for this imbalance man/woman that is found
In all studies. In the French study, the median age of patients was
72 years (from 30 to 92). Some publications suggested that
have been an increase in the cases of LCM since the last decade. It is
Hard to say for sure.

To date, there have been no evidence of environmental factors that promote
The occurrence of the LCM. Despite the absence of risk factors specifically
Recognised, it is recognized that autoimmune diseases would promote
Of this type of lymphoma. The role of some infectious agents (viruses,
Bacteria...) Remains to be demonstrated, as is the impact of pesticides [3].
Oncogenesis
The T (11; 14) (q13; q32) is the initial oncogenic event but not sufficient
Responsible for the development of a LCM [4]. T (11; 14) occurs at the level
Of an immature B cell when recombining the VDJ segments. The pathology
Develops at a later stage of lymphopoietic B since the equivalent of
Non-tumor cell is a naïve CD5 + B cell located in the area of the
Coat. The germ pre-center nature of the tumor cell is demonstrated
By the low frequency of somatic mutations of the gene encoding the part
Variable of the heavy chain of immunoglobulins.
T (11; 14) juxtaposes the gene encoding cyclin D1 (CCND1), located at the
Level of chromosome 11, near the gene encoding the heavy chain
of immunoglobulins located at the level of chromosome 14. T (11; 14)
is directly responsible for increasing the expression of the protein
Cyclin D1, which will lead to cascade deregulation of the Via cell cycle,
Among other things, the phosphorisation of the Rb protein responsible for the release of
The E2F protein. Other anomalies amplify the message Promitotique
Generated by the cyclin D1 leading to the transition of the G1 phase cell
In the S-phase (Fig. 1). In addition to the increase in the expression of the cyclin D1,
Major pathways of the cycle such as INK4A/CD4-4/RB1 and ARF/
MDM2/TP53 are frequently altered, as is the expression of small
Cycle proteins (P27). The amplification of the Promitotique message promotes
Uncontrolled cell proliferation independent of the control points of the
The nesting cycle of highly responsible chromosomal and gene instability
Other anomalies. Among all the chromosomal anomalies described
In the LCM some are recurrent, there are also many anomalies
Number of chromosomes than gains (3q, 6p, 7p, 8q, 10P13, 12q, and 18q)
Or losses (chromosomes 1p, 6p, 8p, 9p, 9q, 10p, 11q14, del13). As in
Many other tumors, there may be deletions of the 17p chromosome or