Evolvement of a five-way translocation t(5;9;22;6;17) from a four-way Philadelphia translocation t(5;9;22;6) in a rare case of chronic myeloid leukemia / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To trace a rare case of chronic myeloid leukemia (CML) with a four-way Philadelphia chromosome variant by cytogenetic analysis in order to provide a basis for the selection of treatment.@*METHODS@#Bone marrow morphology, chromosomal karyotyping, fluorescence in situ hybridization (FISH) and real-time quantitative PCR (RQ-PCR) were used for the diagnosis and staging of the disease. Point mutations in the tyrosine kinase domain of ABL1 gene were detected by Sanger sequencing.@*RESULTS@#The patient was initially diagnosed as CML in chronic phase (CML-CP) with a chromosomal karyotype of 46,XX,t(5;9;22;6)(q13;q34;q11;q25), while FISH revealed presence of a variant Philadelphia chromosome translocation. Clonal evolution has occurred after 38 months of tyrosine kinase inhibitor (TKI) treatment, when cytogenetic analysis revealed coexisting t(5;9;22;6)(q13;q34;q11;q25) and t(5;9;22;6;17)(q13;q34;q11;q25;q11). After 57 months of TKIs treatment, only the t(5;9;22;6;17) clone was detected. Three months later, hyperdiploidy with additional abnormalities were detected in addition to t(5;9;22;6;17). Three mutations, including p.Tyr253Phe, p.Thr315Ile and p.Gly250Glu, were identified in the tyrosine kinase domain of the ABL1 gene during the course of disease. The patient did not attain cytogenetic and molecular response to TKIs.@*CONCLUSION@#The four-way variant translocation may be genetically unstable. Clonal evolution and genetic mutations are likely to occur during TKIs treatment, resulting in poor response to drug therapy. This observation, however, needs to be confirmed by large-scale studies.