title: Assessment of Molecular Markers in AML Patients: A Hospital-Based Study in Lebanon.
abstract: BACKGROUND
  In the past, research has been focused on elucidating the molecular genetics and epigenetic basis of acute myelogenous leukemia (AML). This has led to the change in the classification and management of AML patients. Because no molecular studies regarding AML characterization in Lebanese patients had yet been reported, we decided to determine in our institution the prevalence of the recurrent genetic rearrangements t(8;21), inv(16), t(15;17) and Fms-like (Suzanne McDonough feline sarcoma) tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) mutations.
  
  
  METHODS
  Fusion gene transcripts from chromosome aberrations were analyzed according to standardized reverse transcription polymerase chain reactions after the report of BIOMED-1 concerted action: investigation of minimal residual disease in acute leukemia. FLT3 and NPM1 mutations were screened using home-brew methodologies.
  
  
  RESULTS
  We reviewed 144 bone marrow samples from AML patients referred to Saint George Hospital for molecular and cytogenetic studies from September 2006 to July 2014. The male to female patient ratio was 1.34 to 1. We detected the inv(16) in 6 patients [4.2%] (type A, 5 [83%]; type D, 1 [17%]), t(8;21) in 7 patients [4.9%] (e5e2), and t(15;17) in 36 patients [25.0%] (24 [67%] breakpoint cluster region 1 (bcr1), 12 [33%] bcr3). Other chromosomal abnormalities (trisomy 8, complex karyotype, t(6;9),…) were found in 44 patients [31.4%] and 51 [35.5%] cases showed normal karyotype. Among the normal karyotypes, 6 patients [11.8%] were FLT3-positive (4 [67%] internal tandem duplication [ITD], 2 [33%] D835V), 8 [15.7%] had type A NPM1 mutation and 8 [15.7%] type A NPM1 and FLT3/ITD concomitantly.
  
  
  CONCLUSIONS
  Our results, except for the prevalence of acute promyelocytic leukemia, are concordant with those reported in the literature with approximately 35% of the patients cytogenetically normal. Testing patients with normal karyotype for other molecular markers such as CCAAT/enhancer-binding protein alpha mutations, isocitrate dehydrogenase 1/2 mutations, and mixed lineage leukemia rearrangements could therefore provide additional prognostic, predictive, and therapeutic values for AML patients.
authors: Department of Hematology/Oncology, Saint George Hospital University Medical Center, Beirut, Lebanon. Electronic address: halabilayal@hotmail.com.
authors: Layal
authors: L
authors: El Halabi
authors: Laboratory Department, Saint George Hospital University Medical Center, Beirut, Lebanon.
authors: Isabelle
authors: I
authors: Djaffar-Jureidini
authors: Laboratory Department, Saint George Hospital University Medical Center, Beirut, Lebanon.
authors: Noha
authors: N
authors: Hakime
authors: Department of Hematology/Oncology, Saint George Hospital University Medical Center, Beirut, Lebanon.
authors: Ghada
authors: G
authors: Saidy
authors: Department of Hematology/Oncology, Saint George Hospital University Medical Center, Beirut, Lebanon.
authors: Nabil
authors: N
authors: Chamseddine
mesh_terms: D015415:Biomarkers; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D059785:Karyotype; D007861:Lebanon; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D009154:Mutation; D000090243:Nucleophosmin; D015995:Prevalence; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D000090243:Nucleophosmin
keywords: Karyotype; Prevalence; Prognosis; Signaling Pathways; Targeted therapy