engleski

Quantitative assessment of minimal residual disease in AML carrying NPM1 mutation A

Objective: AML harboring NPM1 mutation causing aberrant cytoplasmic expression of nucleophosmin accounts for approximately 30% of adult AML and shows a favorable prognosis, in the absence of FLT3 -ITD mutation. Detecting this mutation is very important in AML with normal karyotype as it represents the only tool for monitoring disease at molecular level. The aim of this study was quantitative assessment of minimal residual disease in AML carrying NPM1 mutation A. Methods: The study included 7 adult patients with mutated NPM1 , 5 females and 2 males, median age 51 (34-62) years with normal karyotype. Real-time quantitative PCR was used to determine NPM1 mutation A (Ipsogen, France) and reverse transcription PCR for FLT3 /ITD mutation detection (Nakao et al, Leukemia 1996). Quantification was performed at diagnosis and in follow up bone marrow samples during 1- 25 (median 12) months. Result: Mutated NPM1 normalized copy number median was 44789 (7532-73276) at diagnosis and 32.7 (0- 377.4) after induction therapy. Follow up samples after consolidation were available for 2 patients, one of them remained slightly positive (mutated NPM1 normalized copy number 9.2) and one was negative after induction therapy. Two out of 7 patients who were among patients with the highest mutated NPM1 normalized copy number at diagnosis (69249 and 60739) were also positive for FLT3 /ITD mutation that converted negative in one patient after consolidation therapy with still measurable mutated NPM1 . Number of leucocytes in pheripheral blood and blasts in bone marrow at diagnosis were not predictors of NPM1 normalized copy number at diagnosis or FLT3/ITD mutation status (see Table I). Conclusion: In conclusion, NPM1 mutation is not only stratification risk factor but also a good tool for minimal residual disease follow up and for prediction of molecular remission.

AML ; NPM1 mutation

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