Soluble phosphorylated fms-like tyrosine kinase III. FLT3 protein in patients with acute myeloid leukemia (AML).
FLT3 ligand (FL) has a significant role in the proliferation and differentiation of hematopoietic cells. Mutations in the FLT3 receptor gene have been reported in 30% of patients with AML. We investigated whether abnormal phosphorylation of FLT3 may be more common in AML. We evaluated FLT3 protein and its phosphorylation in the plasma from 85 patients with AML, 16 patients with myelodysplastic syndrome (MDS) and 5 patients with acute lymphoblastic leukemia (ALL). There were no significant differences in the level of plasma FLT3 protein level in the different diseases (p=0.57). AML patients had a significantly higher level of phospho-FLT3:FLT3 ratio (p=0.02). FLT3-ITD and FLT3 point mutations were present in 27 (32%) of the AML patients. Phosphorylated FLT3 was significantly higher in the plasma from patients with FLT3 mutation (p=0.002). Overall, there was no correlation between survival and the plasma level of FLT3 protein or its phosphorylated form. However, amongst the patients without FLT3 mutations, those with a higher level of phosphorylated FLT3 had a significantly shorter duration of remission (p=0.04). Other mechanisms may be responsible for abnormal phosphorylation of FLT3 and inhibitors of FLT3 should also be investigated in patients without mutations.
Ravandi
F
F
Leukemia Department, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. fravandi@mdanderson.org
Jilani
I
I
Estey
E
E
Kantarjian
H
H
Dey
A
A
Aguilar
C
C
Jitkaroon
C
C
Giles
F
F
O'Brien
S
S
Keating
M
M
Albitar
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D006412:Hematopoietic Stem Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000628:therapy; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000628:therapy; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012074:Remission Induction; D051941:fms-Like Tyrosine Kinase 3 / Q000097:blood* / Q000235:genetics
D008565:Membrane Proteins; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3