Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature

Diwakar Sharma; Christine Wilson; Sachin Kumar; Sampa Ghose; Ranjit Sahoo; Surender K Sharawat

doi:10.1016/j.anndiagpath.2024.152303

Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature

Ann Diagn Pathol. 2024 Apr 9:71:152303. doi: 10.1016/j.anndiagpath.2024.152303. Online ahead of print.

Authors

Diwakar Sharma¹, Christine Wilson¹, Sachin Kumar¹, Sampa Ghose¹, Ranjit Sahoo¹, Surender K Sharawat²

Affiliations

¹ Department of Medical Oncology, Dr.B.R.A. I.R.C.H., All India Institute of Medical Sciences, New Delhi, India.
² Department of Medical Oncology, Dr.B.R.A. I.R.C.H., All India Institute of Medical Sciences, New Delhi, India. Electronic address: sksharawat@gmail.com.

PMID: 38636337
DOI: 10.1016/j.anndiagpath.2024.152303

Abstract

Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more chromosomes. The outcome of treating patients harbouring complex Ph-positive cytogenetics with tyrosine kinase inhibitors (TKI) is unclear. In the present systematic review, we aim to summarise the response of patients with complex Ph-positive cytogenetics to treatment with TKI therapy. We collated all available literature from databases such as PubMed, Google Scholar, Web of Science database, Cochrane library, Scopus and Embase (up until January 31st, 2024), which describe cases of patients with CML, harbouring complex Ph-positive variations (three and four-way translocations), and summarised their response to TKI therapy. The studies were screened for the following criteria: documented TKI intervention and outcome (whether CR was achieved). Studies that did not report the same, were excluded. Additionally, we report a case from our center of a 55-year-old patient with CML, positive for the Ph-chromosome, harbouring a three-way translocation involving chromosome 15 i.e. 46XX, t(9;15;22) (q34;p11;q11). Identification of BCR::ABL and involvement of chromosome 15 was carried out using conventional cytogenetics, fluorescence in situ hybridization (FISH), and quantitative PCR (qPCR). Based on the inclusion criteria, a total of 15 studies were included from which a total of 87 cases were covered. Overall, we identified 38 unique complex three- and four-way translocations across 87 Ph-positive cases and found that 85 patients with complex Ph-positive cytogenetics achieved complete remission upon treatment and did not appear to have a lesser response to TKI therapy.

Keywords: BCR::ABL1 fusion gene; Chronic myeloid leukemia; Conventional cytogenetics; FISH; qPCR; t(9;15;22) translocation.

Publication types

Review