Chronic myelogenous leukemia (CML) is a hematological malignancy that is a result of a genetic translocation of 2 genes on chromosomes 9 and 22. This translocation, denoted t(9;22)(q34;q11) leads to the creation of the Philadelphia (Ph) chromosome, which produces the BCR-ABL1 fusion gene. The BCR gene is located on chromosome 22 while the ABL1 gene comes from chromosome 9. The product of the BCR-ABL1 fusion gene is a protein that has increased tyrosine kinase activity compared with the typical ABL1 product.1 This increased tyrosine kinase activity leads to upregulated and uncontrolled production of mature granulocytes including mostly neutrophils, but also eosinophils and basophils.
Close to 50% of patients with CML can be asymptomatic and only have early findings of disease found on routine labs such a complete blood count.2 Patients who develop symptoms can experience fatigue, weight loss, sweating (especially at night), bleeding, lymphadenopathy, abdominal pain, and early satiety.2 Whether or not patients develop symptoms can be based on which of the three phases of CML they are in: chronic phase (CP), accelerated phase (AP), or blast crisis (BC). CML treatment varies depending on what phase the patient is in and can include stem cell transplantation, tyrosine kinase inhibitors (TKIs), and other chemotherapy such as cytarabine.3 TKIs have become the mainstay of CML treatment, with agents such as imatinib that primarily focus on inhibiting the BCR-ABL1 protein in the chronic phase. Newer TKIs include nilotinib, dasatinib, and bosutinib.
As the drug-development landscape continues to expand in CML, new genetic targets are being studied. Some patients will inevitably lose response to TKIs, therefore, there is increasing research aimed at understanding why, and if there are new potential drug targets that could help these patients.
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Despite the Ph chromosome being the predominant chromosomal aberration driving the underlying problems, health care practitioners are researching additional chromosomal abnormalities (ACAs) that could also provide useful in the treatment cascade. These ACAs could explain why and when certain patients with CML progress through the different phases and eventually become resistant to certain treatments.4,5
When patients develop ACAs, it is believed to represent “clonal evolution” of the disease; this field of research is gaining momentum. 6 Traditionally, ACAs have been found to be more common in patients in the BC compared with those who are in CP or AP.7
To further elucidate the ACAs and their impact on disease progression, a recent study was conducted and published by Chandran and colleagues.6 The authors conducted chromosomal analysis using GTG-banding, fluorescent in situ hybridization (FISH), and spectral karyotyping (SK) of 489 patients from a single center in India who tested positive for the BCR-ABL1 fusion gene (median patient age was 43 years; range, 15-75 years).
