BACKGROUND AND OBJECTIVES: A partial tandem duplication within the MLL-gene (MLL-PTD) can be found in 8% of all patients with karyotypically normal acute myeloid leukemia (AML), a group in which polymerase chain reaction-(PCR) based minimal residual disease analysis has not, so far, been possible. DESIGN AND METHODS: A sensitive real-time PCR assay to quantify MLL-PTD transcripts was established and expression ratios assessed in diagnostic and follow-up samples. The prognostic significance of MLL-PTD expression levels was evaluated in 145 MLL-PTD positive patients at diagnosis and in 44 patients during and after treatment. RESULTS: Paired samples from 16 patients evaluated at diagnosis and relapse for the presence of the MLL-PTD were analyzed in parallel and all samples were positive at both time points. Overall, 173 samples from 44 patients were analyzed during follow-up (median sample number: 4/patient (range 2-17)). Nineteen patients were evaluable for MRD within the first 2 months, 15 patients within 4 months, and 19 patients within 6 months after the start of therapy. A >or= 2 log reduction of MLL-PTD expression in comparison to < 2 log reduction within 2, 4, and 6 months after start of therapy was found to be significantly associated with longer overall survival (p=0.029, p=0.007, and p=0.022, respectively). A molecular relapse was detected in 2 cases, in each case preceeding clinical manifestation by 35 days. INTERPRETATION AND CONCLUSIONS: These data suggest that MLL-PTD is a stable marker and can be used as a prognostically important marker of MRD in patients with karyotypically normal AML.
BACKGROUND AND OBJECTIVES: A partial tandem duplication within the MLL-gene (MLL-PTD) can be found in 8% of all patients with karyotypically normal acute myeloid leukemia (AML), a group in which polymerase chain reaction-(PCR) based minimal residual disease analysis has not, so far, been possible. DESIGN AND METHODS: A sensitive real-time PCR assay to quantify MLL-PTD transcripts was established and expression ratios assessed in diagnostic and follow-up samples. The prognostic significance of MLL-PTD expression levels was evaluated in 145 MLL-PTD positive patients at diagnosis and in 44 patients during and after treatment. RESULTS: Paired samples from 16 patients evaluated at diagnosis and relapse for the presence of the MLL-PTD were analyzed in parallel and all samples were positive at both time points. Overall, 173 samples from 44 patients were analyzed during follow-up (median sample number: 4/patient (range 2-17)). Nineteen patients were evaluable for MRD within the first 2 months, 15 patients within 4 months, and 19 patients within 6 months after the start of therapy. A >or= 2 log reduction of MLL-PTD expression in comparison to < 2 log reduction within 2, 4, and 6 months after start of therapy was found to be significantly associated with longer overall survival (p=0.029, p=0.007, and p=0.022, respectively). A molecular relapse was detected in 2 cases, in each case preceeding clinical manifestation by 35 days. INTERPRETATION AND CONCLUSIONS: These data suggest that MLL-PTD is a stable marker and can be used as a prognostically important marker of MRD in patients with karyotypically normal AML.
Authors: M-T Krauth; C Eder; T Alpermann; U Bacher; N Nadarajah; W Kern; C Haferlach; T Haferlach; S Schnittger Journal: Leukemia Date: 2014-01-09 Impact factor: 11.528
Authors: Ilaria Iacobucci; Ji Wen; Manja Meggendorfer; John K Choi; Lei Shi; Stanley B Pounds; Catherine L Carmichael; Katherine E Masih; Sarah M Morris; R Coleman Lindsley; Laura J Janke; Thomas B Alexander; Guangchun Song; Chunxu Qu; Yongjin Li; Debbie Payne-Turner; Daisuke Tomizawa; Nobutaka Kiyokawa; Marcus Valentine; Virginia Valentine; Giuseppe Basso; Franco Locatelli; Eric J Enemark; Shirley K Y Kham; Allen E J Yeoh; Xiaotu Ma; Xin Zhou; Edgar Sioson; Michael Rusch; Rhonda E Ries; Elliot Stieglitz; Stephen P Hunger; Andrew H Wei; L Bik To; Ian D Lewis; Richard J D'Andrea; Benjamin T Kile; Anna L Brown; Hamish S Scott; Christopher N Hahn; Paula Marlton; Deqing Pei; Cheng Cheng; Mignon L Loh; Benjamin L Ebert; Soheil Meshinchi; Torsten Haferlach; Charles G Mullighan Journal: Nat Genet Date: 2019-03-29 Impact factor: 38.330
Authors: M-T Krauth; T Alpermann; U Bacher; C Eder; F Dicker; M Ulke; S Kuznia; N Nadarajah; W Kern; C Haferlach; T Haferlach; S Schnittger Journal: Leukemia Date: 2014-08-11 Impact factor: 11.528
Authors: Tara K Gregory; David Wald; Yichu Chen; Johanna M Vermaat; Yin Xiong; William Tse Journal: J Hematol Oncol Date: 2009-06-02 Impact factor: 17.388