Cytogenetics of Leukemia

Abstract

Introduction The study of chromosomes in leukemia has contributed significantly to understanding the biology of the disease, including both some of the molecular (genetic) aberrations involved in pathogenesis and prediction of response to treatment. Cytogenetic aberrations in malignancy can be either primary or secondary (1,2). Primary aberrations are believed to be pathogenic and thus tend to be disease-specific (1). Secondary aberrations are superimposed upon the primary aberrations and may contribute to disease progression; they are less disease-specific, and the same abnormality may occur as a secondary abnormality in various malignancies (2). This article will discuss the primary cytogenetic aberration associated with chronic myelogenous leukemia (CML), some of the primary cytogenetic aberrations that occur in acute leukemia, both nonlymphocytic (ANLL) and lymphocytic (ALL), the molecular aberrations that give rise to these chromosomally visible alterations, and the prognostic significance of the cytogenetic/molecular abnormalities. At the molecular level, these abnormalities frequently involve “oncogenes,” normal cellular genes (proto-oncogenes) that when aberrantly expressed contribute to neoplasia. These genes usually have a dominant mode of action and affect cell growth, differentiation, or death. Although only a few are known to be pathogenic in leukemias, tumor suppressor genes (TSG) also may be affected by chromosomal abnormalities. The normal function of most TSG is in control of cell division. They are recessive in most tumors, and both alleles must be inactivated for an effect on tumorigenesis.