Molecular Monitoring of BCR-ABL Transcripts—Standardization Needed to Properly Use, and Further Investigate the Value of, a Critical Surrogate Marker for Success in Therapy of Chronic Myeloid Leukemia

Abstract

Targeted inhibition of the oncogenic function of the constitutively active BCR-ABL kinase with tyrosine kinase inhibitors is a highly effective and now standard therapeutic approach for patients with chronic myeloid leukemia. The early evaluation of response during the course of therapy is important for determining whether therapy is progressing according to expectations that correlate with optimal outcome. Therefore, frequent disease monitoring to assess treatment and to detect failure or suboptimal response is recommended. Current monitoring strategies incorporate hematological, cytogenetic, and molecular analysis, the latter involving the quantification of BCR-ABL transcripts in the blood. Molecular monitoring has been shown to be the most sensitive method available and has shown prognostic impact with regard to progression-free survival, but the use of diverse methods to quantify BCR-ABL levels has made it difficult to compare results between (and sometimes within) laboratories, with resulting implications for patient care. This article discusses the current approaches and challenges to BCR-ABL monitoring, summarizes some of the international efforts under way to standardize BCR-ABL analysis, and suggests potential alternative approaches to facilitating reproducible BCR-ABL monitoring results, such as a standardized US Food and Drug Administration-approved BCR-ABL testing kit.