Impact of FLT3 mutations and promyelocytic leukaemia-breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia.
In the present study 170 newly diagnosed acute promyelocytic leukaemia patients (M3: n = 121; M3v: n = 49) were molecularly characterised with respect to PML breakpoint and additional molecular mutations. In total, 83 patients were positive for bcr1 (49%), five for bcr2 (3%) and 82 for bcr3 (48%). Bcr3 was more frequent in M3v (65.3%) compared with M3 (41.3%) (P = 0.005). Cases with bcr3 showed a significantly higher white blood cell count (median: 3.65 x 10(9)/l vs. 1.59 x 10(9)/l, P = 0.003), as well as a higher PML-RARAABL expression ratio (14.8% vs. 72.7%, P < 0.005) compared with bcr1. FLT3-length-mutations were detected more frequently together with bcr3 compared with bcr1 (56.5% vs. 19.4%, P < 0.001) and in M3v compared with M3 (64.5% vs. 24.1%, P < 0.005). FLT3 tyrosine kinase mutations were found in eight cases (6.4%) and were distributed equally within the total group. Analysis for further mutations revealed no MLL-PTD and KIT mutations and only two cases of 99 analysed (2%) with NRAS mutations. FLT3-mutations were detected in 62 of 139 cases (44.6%) and associated with a significant lower overall survival (P = 0.0339). In addition, cases with bcr3 showed a tendency for a worse event-free survival (P = 0.0795) compared with the bcr1 group.
Kuchenbauer
Florian
F
Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig-Maximilians University of Munich, University Hospital Grosshadern, Munich, Germany.
Schoch
Claudia
C
Kern
Wolfgang
W
Hiddemann
Wolfgang
W
Haferlach
Torsten
T
Schnittger
Susanne
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C497970:FLT3 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr