Hematopoietic Cancer Models
Eduardo Rego, Rosa Bernardi, Silvia Grisendi, Michelle Le Beau, David Largaespada, James Downing, Kevin Shannon, Scott Kogan and Pier Paolo Pandolfi
Welcome to the MMHCC Hematopoietic Malignancies Site. Here you will find an overview on blood
neoplastic disorders and their molecular basis. We will also summarize how mouse modeling of
hematopoietic malignancies has contributed to our understanding of the molecular mechanisms
underlying these diseases and offered novel tools for the development of novel therapeutic
approaches.
The development of murine models of hematopoietic malignancies has been particularly successful
in the last few years in view of the detailed knowledge of the molecular basis underlying these
diseases. Furthermore, advanced tools are available for restricting the expression of oncogenic products
to specific hematopoietic compartments in the transgenic mouse and to conditionally
inactivate tumor suppressor genes. More recently, mutant mice have been engineered to recreate
at the somatic level and conditionally the most common type of molecular lesion associated with
leukemias and lymphomas: chromosomal translocations leading to the generation of oncogenic fusion
genes. These models accurately mimic the human condition in which genetic mutations occur in a
subset of cells within the adult somatic tissues. Mouse models of human hematopoietic malignancies
have already been instrumental in unraveling pathogenetic mechanisms as well as in facilitating
the development and testing of novel therapeutic approaches.
The following topics will be discussed:
- Development of the Hematopoietic Tissue
- Classification of Human Hematopoietic Malignancies
- Classification of Hematopoietic and Lymphoid Neoplasms in Mice
- Molecular Characterization of Human Hematopoietic Malignancies
- Genetic Tools for Modeling Leukemia and Lymphoma in the Mouse
- Expression Profiling of Murine Leukemias
- Preclinical Studies
Hematopoietic Malignancies
Hematopoietic malignancies are a heterogeneous group of diseases. The World Health Organization
(WHO) classification of tumors of the hematopoietic and lymphoid tissues is based on the
morphologic, immunophenotypic, genetic and clinical features.
Nine categories
have been recognized:
I) Chronic myeloproliferative diseases
II) Myelodysplastic/ myeloproliferative diseases
III) Myelodysplastic syndromes
IV) Acute myeloid leukemias
V) B-cells neoplasms
VI) T-cell and NK-cell neoplasms
VII) Hodgkin lymphoma
VIII) Histiocytic and dendritic-cell neoplasms
IX) Mastocytosis
Each category is further divided in several subtypes, in order to define entities with distinct clinical/prognostic features.
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