Chromosome abnormalities in leukemia and lymphoma.

Nonrandom chromosome changes have been identified in a number of malignant human tumors. The leukemias are among the best studied malignant cells and they provide the largest body of relevant cytogenetic data. In chronic myeloid leukemia, a reasonably consistent translocation [t(9;22) (q34;q11)] is observed in 93 percent of all Ph1 positive patients. In the other patients, translocations are either two-way, involving No. 22 with some other chromosome or complex translocations involving Nos. 9 and 22 and another chromosome. In acute nonlymphocytic leukemia, two translocations are each specifically associated with leukemic cells arrested at two different stages of maturation. One of these, t(8;21)(q22;q22), is found mainly in patients with acute myeloblastic leukemia with maturation (AML-M2). The other, t(15;17)(q22?;q21?), is seen only in patients with acute promyelocytic leukemia (APL-M3). Various translocations have been observed in B-cell acute lymphoblastic leukemia or in Burkitt lymphoma. The most common is t(8;14)(q24;q32), but variants of this, namely t(2;8)(p13?;q24) and t(8;22)(q24;q11), have also been observed; in all of these, the consistent change involves 8q24. The various immunoglobulin loci are located on chromosomes 2, 14, and 22 in the same chromosome band affected by the translocations in B-cell leukemia. These translocations may occur randomly. If a specific translocation provides a particular cell type with a growth advantage, then selection could act to cause the proliferation of this aneuploid cell line vis-a-vis cells with a normal karyotype. In this view, the chromosome change could be the fundamental event leading to the leukemic transformation of an otherwise normal cell. The challenge for the future is to define the genes located at the sites of consistent translocations in myeloid leukemias and to determine the alterations in gene function that are associated with the translocation.