title: Increased coexpression of c-KIT and FLT3 receptors on myeloblasts: independent predictor of poor outcome in pediatric acute myeloid leukemia.
abstract: BACKGROUND
  Significance of mutations in FLT3 and c-KIT genes in AML has been well established, but role of their coexpression has not been evaluated. The aim of this study was to evaluate clinical significance of FLT3 (CD135) and c-KIT (CD117) coexpression on myeloblasts in AML.
  
  
  METHODS
  Using flow-cytometry, we prospectively observed in 115 AML patients that CD135, CD117, and CD135+CD117 coexpression was expressed in 95 (82%), 104 (90%), and 81 (70%) patients respectively. Median expression of CD135, CD117, and their co expression was used as cut off for high and low expression.
  
  
  RESULTS
  FLT3 ITD (internal tandem duplication) was present in 20 (17%) patients. High coexpression did not correlate with FLT3 ITD (P = 0.432) and cytogenetics (P = 0.244). Out of 115 patients, 86 (74.7%) achieved remission. At median followup of 15.5 months, EFS and OS was 29% and 35%, respectively for the entire cohort. Patients with high coexpression of CD135 and CD117 in comparison to those with low coexpression had significantly inferior EFS (20% vs 38% P < 0.001) and OS (27% vs 44% P = 0.001). In step wise Cox regression multivariable analysis, hazard ratio for high hemoglobin, WBC count, and coexpression of CD135 and CD117 was 0.63, 1.73, and 2.46 respectively for EFS, and for OS only CD135+CD117 coexpression emerged as an independent predictor (hazard ratio 2.25).
  
  
  CONCLUSIONS
  This is the first study to show that high coexpression of CD135+CD117 is an independent predictor of poor outcome in AML and is easily measurable by routine diagnostic flow-cytometry.
authors.affiliation: Department of Medical Oncology, University of Delhi; Dr. B. R.A. Institute Rotary Cancer Hospital, New Delhi, India; All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Surender Kumar
authors.initials: SK
authors.lastname: Sharawat
authors.forename: Ritu
authors.initials: R
authors.lastname: Gupta
authors.forename: Vinod
authors.initials: V
authors.lastname: Raina
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.forename: Atul
authors.initials: A
authors.lastname: Sharma
authors.forename: Sobuhi
authors.initials: S
authors.lastname: Iqbal
authors.forename: Radhika
authors.initials: R
authors.lastname: Bakhshi
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Vishnubhatla
authors.forename: Sameer
authors.initials: S
authors.lastname: Bakhshi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D042381:Granulocyte Precursor Cells / Q000378:metabolism; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute Myeloid Leukemia; CD117; CD135; Coexpression; Flow-cytometry