Chronic myeloid leukemia (CML) patients have a classical cytogenetic abnormality formed by a reciprocal translocation between chromosomes 9q34 and 22q11 also known as the Philadelphia (Ph) chromosome. The t(9;22)(q34;q11) leads to the formation of the BCR::ABL1 (Breakpoint Cluster Region/Abelson 1) fusion gene on the marker chromosome 22 [1]. The t(9;22)(q34;q11) translocation is seen in 90–95 % of CML patients. Variant complex translocations including a third chromosome other than (9;22) have been identified in 5–8 % of individuals [1,2].

CML patients who are Ph-positive receive TKI treatment as first-line therapy [3]. Imatinib mesylate was developed particularly to suppress the tyrosine kinase activity of the BCR/ABL1 protein as well as other tyrosine kinases such as cABL, c-KIT, and platelet-derived growth factor receptor (PDGFR). Imatinib inhibits downstream signalling by attaching to a tyrosine kinase active site, preventing cell growth and triggering apoptosis [4]. Imatinib treatment has shown great effectiveness in attaining a cytogenetic response, i.e., a decrease in Ph-positive cells to 0–35 % [5,6]. However, about 5 % of patients with CML have complex cytogenetic abnormalities including the Ph-chromosome. Here, a third or fourth chromosome may also be involved [7]. The impact of TKI treatments such as imatinib mesylate, on patients harbouring various complex Ph-positive cytogenetics is not clear.

Our objective was to review CML cases harbouring complex Ph-positive variant translocations for whether TKI treatment leads to a response (complete remission) in such cases. In these studies that were compiled, the complex Ph-positive cytogenetics was detected with various detection modalities like conventional cytogenetics, reverse transcriptase polymerase chain reaction (qPCR), and molecular cytogenetics; the fluorescent in situ hybridization (FISH) method. This is the first study to compile a systematic review of the response of patients with CML harbouring variant BCR::ABL1 complex translocations to TKIs.