title: High fms-like tyrosine kinase-3 (FLT3) receptor surface expression predicts poor outcome inFLT3internal tandem duplication (ITD) negative patients in adult acute myeloid leukaemia: A prospective pilot study from India.
abstract: OBJECTIVE
  Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome.
  
  
  METHODS
  Total 51 consecutive de novo AML patients aged 18-60 yr were enrolled in the study. FLT3 ITD was detected by polymerase chain reaction (PCR); flowcytometry and qPCR (Taqman probe chemistry) were used for assessment of FLT3 protein and transcript, respectively. Kaplan Meier curves were obtained for survival analysis followed by log rank test.
  
  
  RESULTS
  FLT3 ITD was present in eight (16%) patients. Complete remission was achieved in 33 (64.6%) patients. At 57.3 months, event free survival (EFS) was 26.9±6.3 per cent, disease free survival (DFS) 52.0±9.2 per cent, and overall survival event (OS) 34.5±7.4 per cent. FLT3 surface expression was positive (>20%) by flow-cytometry in 38 (88%) of the 51 patients. FLT3 surface expression and transcripts were not associated with FLT3 ITD status. FLT3 expression was significantly associated with inferior EFS (P=0.026) and OS (P=0.018) in those who were negative for FLT3 ITD.
  
  
  CONCLUSIONS
  This study evaluated FLT3 ITD mutation along with FLT3 expression in AML patients, and associated with survival. Negative impact of FLT3 surface expression on survival was observed in AML patients who were FLT3 ITD negative.
authors.affiliation: Department of Medical Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Surender Kumar
authors.initials: SK
authors.lastname: Sharawat
authors.affiliation: Department of Medical Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Raina
authors.affiliation: Department of Medical Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.affiliation: Department of Medical Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Biomedical Sciences, Shaheed Rajguru College of Applied Sciences, University of Delhi, Delhi, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Bakhshi
authors.affiliation: Department of Biostatistics, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Vishnubhatla
authors.affiliation: Laboratory Oncology Unit, Dr B.R.A. Institute Rotary Cancer Hospital, AIIMS, New Delhi, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Medical Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bakhshi
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007194:India; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D020080:Tandem Repeat Sequences / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3