Chimeric genes in acute leukemias

In this thesis the genetic analysis of two types of acute leukemia characterized by translocations will be described. Both translocations generate chimeric genes which are specific for these subtypes of leukemia. The non-random changes that occur at the molecular level can be used in addition to karyotyping to diagnose the presence of tumor cells. The linkage of specific subtypes of acute myeloid leukemia with t(6;9) to a consistent rearrangement involving the ~-gene on chromosome 6 and the g.n-gene on chromosome 9 will be shown (Chapters III.2 and ill.3). This is of clinical importance since a correct diagnosis and subclassification indicates the prognosis of the diaease and helps to choose the right therapy, thereby improving the prognosis for a patient. The second type of acute leukemia that will be discussed is the acute lymphoblastic leukemia associated with the t(9;22). Here, rearrangement of genes results in a chimeric bcr-abl gene on the Philadelphia chromosome. A variant of this chimeric gene was found and analyzed (Chapter II.3). The study of altered genes in leukemia provides us with a multitude of questions conceroing their function and role in the origin of the tumor. However, unusual variants of tumor-specific products may help to solve parts of the mystery of tumor formation.