BRIEF REPORT |
Correspondence to: Eric D. Hsi, Dept. of Clinical Pathology, L-11, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. E-mail: hsie@ccf.org
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Summary |
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Beginning with the discovery of the Philadelphia chromosome in 1960, our descriptions and definitions of hematological malignancies have been successively refined and revised to include morphological, immunophenotypic, and molecular genetic features. As hematopathologists, we now see beyond architectural and cytologic alterations and have, to some degree, become molecular morphologists. Indeed, our "view" of diseases now includes a rudimentary understanding of the molecular genetic abnormalities present in the cells we study under the microscope. (J Histochem Cytochem 49:13231324, 2001)
Key Words: hematological malignancy, leukemia, lymphoma, molecular hematopathology
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Introduction |
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THE UPCOMING World Health Organization (WHO) classification of hematolymphoid malignancy reflects our attempts to define diseases at the molecular level (
Perhaps the two best known examples of this are all-trans retinoic acid (ATRA) for AML-M3 with the t(15;17) and the tyrosine kinase inhibitor STI-571 in CML. The t(15:17) results in the fusion of the zinc finger-containing gene PML and nuclear hormone receptor RAR gene (
Although specific therapies are not as far advanced in the area of mature B-lymphoid malignancies, significant progress is being made in the molecular genetic classification of disease. Two examples include B-cell chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). In CLL, two subtypes have recently been defined based on mutational status of the immunoglobulin heavy chain (IgH) gene. Cases demonstrating somatic mutation, similar to post-germinal center B-cells, have a significantly better survival than those with germline IgH genes (
These examples illustrate our movement into a new era of molecular genetic classification, molecular diagnosis, and rational drug design in hematological malignancy. They may be seen as paradigms for the application of molecular genetic tools to help separate and define distinct diseases. The unique patterns of tumor gene expression (transcriptomes) and protein expression (proteomes) may then serve as the basis for developing targeted therapies for these molecularly defined entities.
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Footnotes |
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Presented in part at the Joint Meeting of the Histochemical Society and the International Society for Analytical and Molecular Morphology, Santa Fe, NM, February 27, 2001.
Received for publication December 26, 2000; accepted February 16, 2001.
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