UPDATE ON SPOT ON CML

• Published in: Anticancer research 2019-10, Vol.39 (10), p.5834
• Main Authors: Torra, Olga Sala, Beppu, Lan, Felton, Catherine, Monroe, Luke, Radich, Jerald P
• Format: Article
• Language: English
• Subjects: BCR-ABL protein; Blood; Cancer; Chromosome aberrations; Collaboration; Developing countries; Fusion protein; Kinases; LDCs; Leukemia; Medical research; Monitoring; Mutation; Peripheral blood; Polymerase chain reaction; Protein-tyrosine kinase; Tyrosine
• ISSN: 0250-7005; 1791-7530

Background: All chronic myeloid leukemias (CML) have the chimeric breakpoint cluster region-abelson (BCR-ABL) fusion gene resulting from the t(9;22) chromosomal abnormality. BCR–ABL mRNA is the basis of reverse transcriptionpolymerase chain reaction (RT-PCR) assays for diagnosis and monitoring. Tyrosine kinase inhibitors (TKIs) can target BCR– ABL and drastically improve outcome for patients with CML. Optimal care in CML requires peripheral blood monitoring of BCR–ABL in order to assess response, and mutation analysis of ABL's tyrosine kinase domain if resistance to TKIs develops. Access to TKIs and molecular diagnostics is limited in developing countries. 'Spot on CML', a collaboration between the Fred Hutchinson Cancer Research Center, The Max Foundation, Cepheid, and the International CML Foundation, started in September 2017 to facilitate access to testing for CML to developing countries. In some countries, patients diagnosed with CML can receive free TKI treatment through Max Foundation's partnership with Novartis and other pharmaceutical companies. Materials and Methods: Patients' dried blood spots (DBS) are sent to the Fred Hutchinson Cancer Research Center. Testing for BCR–ABL mRNA is carried out using lysate and Cepheid GeneXpert platform. ABL mutations are assayed by Sanger sequencing. We demonstrated the accuracy of DBS in head-to-head comparisons with standard peripheral blood testing (1). Results: Since September 2017, we have received specimens for 463 patients from 21 institutions in 19 countries in Central and South America, Asia, Africa and Oceania. A total of 449 specimens were submitted for detection/quantification of BCR–ABL and 12 for mutation analysis, with all specimens proving adequate for analysis. Overall, 348 specimens were positive for BCR–ABL (75.3%) at levels ranging from 0.0038% to 110%. No ABL mutations were detected. Regular updates for this project are posted on: https://spotoncml.shinyapps.io/SPOTonCML/. Conclusion: SPOT on CML is a collaboration that effectively provides testing for CML in developing countries. The use of DBS is cost-effective: batches of samples can be sent to a central laboratory by slow but inexpensive transportation.