Chronic myeloid leukemia: Relevance of cytogenetic and molecular assays

• Ph negative and variant Ph rearrangements are diagnosed with cytogenetic tests.
• Additional abnormalities in Ph+/−karyotype are revealed by conventional cytogenetic.
• Conventional and molecular cytogenetic are the standard tests for diagnosis of CML.
• Quantitative PCR is the standard test for molecular monitoring of CML.
• The cytogenetic and molecular responses are the gold standards of CML therapy.

Chronic myeloid leukemia (CML) is the prototype cytogenetic malignancy. Even before the development of basic G- and R-banding techniques, CML was found to be associated with a persistent chromosomal abnormality, the Philadelphia (Ph) chromosome. Banding technology later showed the marker chromosome to be a translocation between the breakpoint cluster region (BCR) on chromosome 22q11.2 and the Abelson proto-oncogene (ABL) on chromosome 9q34. Further advances in cytogenetic and molecular biology have also contributed to the understanding, diagnosis, and treatment of CML. Fluorescent in situ hybridization (FISH) has revealed cryptic translocations in most cases of Ph-negative CML. Additional rare chromosomal variant translocations have been discovered as well.The understanding of cytogenetic and molecular physiopathology of CML has led to the use of tyrosine kinase inhibitors as treatment for this disease with spectacular success. Over the 40 years since being identified as the first cytogenetic disease, CML has become the greatest success in translating the basic science of oncology into the treatment of patients with cancer.In this review we will not only summarize the biology of CML, recent progress in the delineation of mechanisms and treatment strategies, but also we will discuss the laboratory tools used for diagnosing CML, for monitoring during treatment and for revealing point mutations and additional chromosomal abnormalities. In doing so, we will describe in detail our individual research on CML, identifying why and how these tests were performed to help to explain CML subgroups and clinical significance of additional chromosomal abnormalities.