Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients.
BACKGROUND
The FLT3 gene is frequently mutated in acute myeloid leukemia (AML), either by an internal tandem duplication (ITD) of the juxtamembrane domain or by activating point mutations in the second tyrosine kinase domain (ATKD). Only a few investigations have focused on the prognostic significance of FLT3 alterations in AML among the elderly, yielding conflicting results. In the present study, the frequency and clinical relevance of FLT3 abnormalities were ascertained in a cohort of elderly AML patients.


METHODS
A total of 109 AMLs, occurring in patients above the age of 60 yr (median 71.5), were investigated. DNA was extracted from fresh bone marrow cells or from cells in fixative and investigated for the presence of ITD of exons 14 and 15 and the ATKD D835 in exon 20.


RESULTS
ITDs and ATKDs were identified in 20 (18%) and 11 (10%) of the cases, respectively. Three cases displayed both an ITD and an ATKD. FLT3 abnormalities were associated with leukocytosis (ITD P < 0.01; ATKD P = 0.069), and the monocytic FAB subtypes M4 and M5 [ITD (P < 0.05), ATKD (P = 0.05)], and ITD and ATKD were significantly (P < 0.05) more common in cases with a normal karyotype. There was no correlation between the presence of FLT3 abnormalities and complete remission rates or overall survival.


CONCLUSIONS
A correlation was observed between FLT3 abnormalities and leukocytosis, a normal karyotype, and the M4/M5 subtypes of leukemia. However, no clear-cut prognostic impact of FLT3 abnormalities was identified in elderly AML patients.
Andersson
Anna
A
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. anna.andersson@klingen.lu.se
Johansson
Bertil
B
Lassen
Carin
C
Mitelman
Felix
F
Billström
Rolf
R
Fioretos
Thoas
T
D000208:Acute Disease; D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D007948:Leukemia, Monocytic, Acute / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D017354:Point Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D016019:Survival Analysis; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3