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Impact of FLT3 mutations and promyelocytic leukaemia‐breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia
Author(s) -
Kuchenbauer Florian,
Schoch Claudia,
Kern Wolfgang,
Hiddemann Wolfgang,
Haferlach Torsten,
Schnittger Susanne
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05595.x
Subject(s) - acute promyelocytic leukemia , medicine , breakpoint , neuroblastoma ras viral oncogene homolog , gastroenterology , mutation , overall survival , white blood cell , biology , gene , genetics , cancer , kras , chromosomal translocation , retinoic acid , colorectal cancer
Summary 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 × 10 9 /l vs. 1·59 × 10 9 /l, P = 0·003), as well as a higher PML ‐ RARA ABL 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.