Differentiation mechanisms and malignancy.
This review considers the relationship between differentiation mechanisms and the genesis and maintenance of tumor phenotype. To a certain extent, carcinomas preserve differentiation markers of normal tissue, and hemoblastoses precisely reflect the direction and differentiation level of their precursor cells. Both tumor types retain the ability to differentiate. Mechanisms of T and B cell differentiation are reviewed considering the activation of protooncogenes by translocation to the region of tissue-specific genes including the immunoglobulin (Ig) and T cell receptor (TCR) genes. Apart from the classical oncogenes (MYC, PRAD, BCL-2), heterologous differentiation of trans-factors can be activated in a similar manner. Their activation at inappropriate time and place induces oncogenic transformation in a number of hemoblastoses. Chimeric genes and fused proteins are analyzed, including their genesis by specific translocation resulting in transformation and their role in differentiation and maintenance of the tumor phenotype. Induction of terminal differentiation in leukemia can have significant therapeutic effect. These hemoblastoses include hairy cell leukemia, promyelocytic leukemia, and in part chronic myeloid leukemia. Specific attention is given to the role of intercellular interactions in the control of tumor growth and maintenance of a differentiated state of the cells. It is suggested that alterations in these interactions during tumor progression simultaneously stimulate malignant growth and decrease differentiation level, thus inducing re-expression of embryonic antigens in the tumors.
Abelev
G I
GI
Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia. abelev@mx.iki.rssi.ru
D002277:Carcinoma / Q000175:diagnosis / Q000473:pathology*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000175:diagnosis / Q000473:pathology; D008223:Lymphoma / Q000175:diagnosis / Q000473:pathology; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D010641:Phenotype; D011993:Recombinant Fusion Proteins
D011993:Recombinant Fusion Proteins