Chronische myeloische Leukämie – Update

Abstract

Chronic myeloid leukemia (CML) is a clonal stem cells disorder and belongs to the myeloproliferative diseases. Over the past decades seminal discoveries in the field of CML research have greatly contributed to our knowledge of leukemogenesis. The hallmark of the disease is the presence of the Philadelphia chromosome, the first described acquired non-random cytogenetic abnormality in human malignancies. This chromosomal abnormality is the result of a reciprocal translocation between chromosomes 9 and 22, t(9;22). At the molecular level this involves the fusion of the ABL protooncogene on chromosome 9 with the BCR (breakpoint cluster region) gene on chromosome 22. The fusion protein has increased tyrosine kinase activity and is a key event in the malignant transformation of a given progenitor cell in the bone marrow. Diagnosis of CML is based on the peripheral blood smear, bone marrow examination, the presence of the Philadelphia chromosome and its molecular correlate, the BCR-ABL transcript. Remarkable progress has been made in the treatment options over the last years which as a result rendered the therapeutic choices more complex and challenging. The current knowledge of treatment options is reviewed with particular emphasis on the newly introduced tyrosine kinase inhibitor Imatinib which opened an as yet unexpected promising avenue in the treatment of CML.