Cytogenetic abnormalities and molecular markers of acute lymphoblastic leukemia

The chromosomal abnormalities that occur in acute lymphoblastic leukemia have greatly elucidated the biologic causes (leukemogenesis) of this disease. ALL is extremely heterogeneous; different cell types at differing stages of differentiation may become leukemic. Although not yet completely understood, the chromosomal abnormalities occurring in this disease are not random. Rather, the abnormalities are highly specific, with specific abnormalities occurring in specific cell phenotypes. Early chromosomal investigations were concerned with identification of heterogeneous cytogenetic "groups," with independent prognostic indications, among patients with ALL. These studies progressed to the identification of specific chromosomal translocations, many of which can be correlated with specific cell phenotypes. Molecular studies of these cytogenetic aberrations have defined specific chromosomal breakpoints, and specific genes, which have been implicated in the oncogenic process. As a result of these translocations, the involved genes either produce abnormal products or are deregulated. The products of these genes vary, but all are concerned with cell growth and differentiation. Much remains to be determined regarding cytogenetic abnormalities in acute lymphoblastic leukemia and their clinical and biologic significance. The molecular bases of all of the recurring abnormalities in ALL have not been determined. The biologic causes for the chromosomal abnormalities are not known, nor is it known why specific chromosomal aberrations correlate with prognosis.