title: Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group.
abstract: Purpose:The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML.Experimental Design:We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children's Oncology Group trial AAML0531.Results:There was high variability in blast CD135 cell-surface expression across specimens. CD135 expression measured by flow cytometry was not correlated with FLT3 transcript expression determined by quantitative RT-PCR. Overall, CD135 expression was not significantly different for patients withFLT3/WT,FLT3/ITD, orFLT3/ALM (P= 0.25). High cell-surface CD135 expression was associated with FAB M5 subtype (P< 0.001),KMT2Arearrangements (P= 0.009), and inversely associated with inv(16)/t(16;16) (P< 0.001). Complete remission rate, overall survival, disease-free survival, and relapse rates were not significantly different between patients with low and high CD135 expression.Conclusions:FLT3 cell-surface expression did not vary byFLT3mutational status, but high FLT3 expression was strongly associated withKMT2Arearrangements. Our study found that there was no prognostic significance of FLT3 cell surface expression in pediatric AML.Clin Cancer Res; 23(14); 3649-56. ©2017 AACR.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. ktarlock@fredhutch.org.|Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tarlock
authors.affiliation: Children's Oncology Group, Monrovia, California.|Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.affiliation: Hematologics, Inc., Seattle, Washington.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loken
authors.affiliation: Children's Oncology Group, Monrovia, California.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington.
authors.forename: Rhonda E
authors.initials: RE
authors.lastname: Ries
authors.affiliation: Division of Hematology/Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario.
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
authors.affiliation: St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.affiliation: Division of Laboratory Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Betsy A
authors.initials: BA
authors.lastname: Hirsch
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Samir B
authors.initials: SB
authors.lastname: Kahwash
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Amy
authors.initials: A
authors.lastname: McKenney
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.affiliation: Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Gamis
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington.
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497422:KMT2A protein, human; D011956:Receptors, Cell Surface; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3