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Heterogeneous Genetic Alterations in CML: Therapeutic Implications

By: Kayci Reyer
Posted: Monday, December 2, 2019

According to a retrospective study published in Cancer Genetics, the development of clonal chromosomal abnormalities in patients with chronic myeloid leukemia (CML) who have Philadelphia chromosome–negative disease may be indicative of a patient group with heterogeneous genetic alterations. In terms of outcomes, Hongyu Ni, MD, PhD, of the University of Illinois at Chicago, and colleagues found that most patients with two or more of these chromosomal abnormalities had an inferior response to tyrosine kinase inhibitors (TKIs).

“Additional studies are needed to define the molecular determinants and long-term implications of this phenomenon,” the investigators suggested.

The single-center study included 24 patients who were identified to have clonal chromosomal abnormalities and Philadelphia chromosome–negative CML during TKI therapy. They all were treated between 2005 and 2015. A total of 18 patients had single cytogenetic abnormalities; 4 had double and 2 had abnormalities deemed complex. Common abnormalities within the group included trisomy 8, monosomy 7, and 20q–. Extensive fluorescence in situ hybridization testing revealed a higher number of double chromosomal abnormalities among the patient population than originally detected by karyotyping alone.

Among patients with double chromosomal abnormalities, all experienced a suboptimal response to treatment, and none achieved a major molecular response. However, all patients with single chromosomal abnormalities responded well to TKIs and achieved a major molecular response

“Further analysis of these CML cases carrying [clonal chromosomal abnormalities/ Philadelphia chromosome–negative disease] with suboptimal response to TKI treatments may help to reveal more molecular mechanisms of TKI resistance,” the investigators concluded.

Disclosure: The study authors reported no conflicts of interest.

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