title: Relative receptor tyrosine kinases and anti-apoptotic transcripts hold potential for predicting inferior outcome in adult acute myeloid leukemia: a prospective pilot study.
abstract: BACKGROUND
  Acute myeloid leukemia is characterized by accumulation of immature cells because of imbalance between proliferation and apoptosis. In AML, simultaneous expression of proliferative (FLT-3, c-KIT) and antiapoptotic genes (BCL-2), are unknown.
  
  
  METHODS
  We prospectively assessed proliferative and antiapoptotic gene transcripts using Taqman probe chemistry in 48 adult AML patients. A stepwise Cox regression model was applied for independent prognostic factors.
  
  
  RESULTS
  Thirty-two of 48 (75%) patients achieved complete remission. At follow-up ranging from 0.5 to 57.3 months, event-free survival (EFS) was 26.9 ± 6.3% (range, 15.5%-39.6%) and OS 34.5 ± 7.46% (range, 20.5%-48.9%). High white blood cell count correlated with an inferior complete remission rate (P = .021). Cytogenetics and FLT-3 internal tandem duplication did not predict EFS or OS. The transcripts of FLT-3, c-KIT, and BCL-2 showed a significant linear association with each other in Pearson correlation (FLT-3 vs. c-KIT: R = 0.8234; P < .001; c-KIT vs. BCL-2: R = 0.3377; P = .01; FLT-3 vs. BCL-2: R = 0.3815; P = .007). In a validation cohort (Microarray Data Set GSE1159) of adult AML patients, the global gene expression profile depicted a similar interrelationship. Patients with a greater platelet count were associated with increased transcript levels of BCL-2 (P = .034). In univariate analysis, a high transcript level of FLT-3 and high transcript ratio of FLT-3/BCL-2 and FLT-3 and c-KIT/BCL-2 significantly predicted OS (P = .043, .028, and .028, respectively). In a stepwise Cox regression model, high FLT-3 and c-KIT/BCL-2 ratio predicted OS (HR, 2.29).
  
  
  CONCLUSIONS
  To our knowledge, this is the first study that evaluated proliferative and antiapoptotic transcripts simultaneously, and results have shown that it is the relative levels of these transcripts that determine outcome in AML patients rather than their expression in isolation.
authors: Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors: Surender Kumar
authors: SK
authors: Sharawat
authors: Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors: Sreenivas
authors: S
authors: Vishnubhatla
authors: Department of Biomedical Sciences, Shaheed Rajguru College of Applied Sciences, University of Delhi, New Delhi, India.
authors: Radhika
authors: R
authors: Bakhshi
authors: Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors: Vinod
authors: V
authors: Raina
authors: Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors: Lalit
authors: L
authors: Kumar
authors: Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors: Atul
authors: A
authors: Sharma
authors: Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. Electronic address: sambakh@hotmail.com.
authors: Sameer
authors: S
authors: Bakhshi
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D015415:Biomarkers; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014158:Transcription, Genetic; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute Myeloid Leukemia; BCL-2; FLT-3; Real-time PCR; c-KIT