Persistence of RARa‐PML fusion mRNA detected by reverse transcriptase polymerase chain reaction in patients in long‐term remission of acute promyelocytic leukaemia

Summary. Acute promyelocytic leukaemia (APL) is characterized by t(15;17), which results in the formation of two chimaeric genes, PML-RARa and RARa-PML. PML-RARa transcripts have been detected in all cases of APL whilst those of RARQ-PML have been detected in only about 67% of cases. We have used reverse transcriptase polymerase chain reaction (RT-PCR) to detect both fusion transcripts serially in 18 patients in remission of APL after chemotherapy and bone marrow transplantation. All patients were negative for PML-RARa, whereas in six patients (remission 3-9 years) RARa-PML was consistently detected. Only one patient at remission showed the 5’breakpoint RARa-PML, with the rest showing the 3’breakpoint 144 bp RARa-PML. The level of sensitivity for detecting RARa-PML was some 10-fold higher than that for PML-RARa. Serial negative tests for PML-RARa have been correlated with durable remissions, suggesting possible eradication of residual leukaemia in APL. Our results, however, show persistence of t(15;17) cells expressing RARa-PML fusion mRNA in patients in long-term remission of APL. They indicate that patients considered clinically‘cured’of APL still have molecular evidence of minimal residual disease and also provide further insight into the biology of acute myeloid leukaemia.